ASCO 2026: 2026-05-29–2026-06-02 (window 2026-05-28–2026-06-03, ±1d) · synthesised from Twitter discussion during the meeting window. No publications this digest.
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In the ITT population, tarlatamab produced a CNS mPFS of NR vs 7.8 months (HR 0.54); in patients with brain metastases, CNS mPFS was 6.5 vs 4.2 months (HR 0.40), CNS complete response rate was 15% vs 5%, and CNS tumor shrinkage ≥30% was achieved in 56% vs 38%. OS in patients with brain metastases was 13.9 vs 6.8 months (HR 0.51), independent of baseline brain metastasis status. Whether these intracranial activity data establish tarlatamab as the second-line standard for SCLC with brain metastases is the central question clinicians are debating.
Discussed by: @StephenVLiu, @diegoadiazg, @g_mountzios
Sunvozertinib delivered an ORR of 58.9% vs 31.1%, median PFS of 10.3 vs 7.5 months (HR 0.65), DOR of 11.2 vs 7.1 months, and 12-month PFS of 46% vs 27% versus chemotherapy. Although grade ≥3 adverse events were more frequent, including diarrhea in 87% (G3+ 14%), no treatment-related deaths occurred. Oncologists are debating whether this oral chemo-free option challenges amivantamab + chemotherapy (PAPILLON) as the frontline standard for EGFR exon20ins NSCLC, noting a high crossover rate from chemotherapy to sunvozertinib in the trial.
Discussed by: @StephenVLiu, @DrMirallas, @diegoadiazg
Neoadjuvant lorlatinib produced an ORR of 83.7%, pCR of 46.9%, MPR of 81.3%, and R0 resection rate of 96.9%, with nodal downstaging in 90.6% of patients. Notably, 75% of initially unresectable patients proceeded to conversion surgery, and 1-year EFS was 97.1%. The open question is whether these deep pathologic responses will translate into improved survival in stage III ALK+ NSCLC.
Discussed by: @HHorinouchi, @StephenVLiu, @diegoadiazg
At 7 years, lorlatinib maintains a median PFS that remains not reached vs 9.1 months (HR 0.19), with a 7-year PFS rate of 55% vs 3%. Intracranial control is equally striking: the 7-year intracranial progression-free rate is 92%, with no new intracranial progression events observed after approximately 30 months. With median PFS still not reached, clinicians are asking whether advanced ALK+ NSCLC is becoming a chronic condition.
Discussed by: @DrMirallas, @StephenVLiu, @OncLive
First-line amivantamab + lazertinib in atypical EGFR-mutated NSCLC yielded an ORR of 57%, median PFS of 19.5 months, and median OS of 41.0 months, with 3-year OS of 55% and 4-year OS of 46%; 20% of patients remained on first-line treatment for up to 4.4 years. Compared with real-world physician-selected EGFR TKIs, median OS was 41.0 vs 15.2 months. The debate centers on whether an mOS of 41 months redefines the gold standard for this population versus historical afatinib.
Discussed by: @HHorinouchi, @Dr_ElvinaA, @StephenVLiu
Adding concurrent thoracic radiotherapy to chemoimmunotherapy in extensive-stage SCLC produced an mOS of 10.0 vs 11.1 months (HR 1.12; 95% CI 0.82–1.54) in one report and mOS 10.0 vs 11.8 months (HR 1.14, p=0.40) in another, with any adverse event rates of 87.8% vs 69.9% and Grade 5 AEs of 14.7% vs 3.5%; the trial was stopped early for futility and excess adverse events. Clinicians are debating whether this negative result closes the door on concurrent thoracic RT in this setting, or whether it is primarily a question of timing.
Discussed by: @M_Torasawa, @HHorinouchi, @DrJNaidoo
In STK11/KEAP1/KRAS-mutated NSCLC, tremelimumab + durvalumab + chemotherapy produced a confirmed ORR of 39.0% vs 34.9% with pembrolizumab + chemotherapy; median duration of response was not reached vs 6.4 months, and 100% vs 58.3% of responders maintained response at 6 months. In KRAS-mutated tumors, ORR was 48.0% vs 33.3%, and the response rate numerically favors dual checkpoint blockade in the STK11 and KRAS subsets, though PFS data remain pending. With PFS still blinded, the discussion among oncologists concerns whether ORR and DoR signals justify CTLA-4 intensification in these immunologically cold subsets.
Discussed by: @diegoadiazg, @StephenVLiu, @Alfdoc2
Sacituzumab tirumotecan + pembrolizumab demonstrated superior PFS versus pembrolizumab alone, with mPFS NR vs 5.7 months (HR 0.35), ORR 70.2% vs 42.0%, and an immature OS HR of 0.55 (95% CI 0.36–0.85) across the PD-L1-positive population (n=413). Subgroup benefit was seen across PD-L1 levels: HR 0.47 in PD-L1 >50% and HR 0.28 in PD-L1 1–49%. Specialists are questioning whether pembrolizumab monotherapy is the appropriate control arm for the PD-L1 1–49% subset, where chemo-IO is considered standard.
Discussed by: @StephenVLiu, @DrMirallas, @BalazsHalmosMD
Upfront cranial radiotherapy significantly improved intracranial control versus delayed RT, with 2-year intracranial progression of 21.7% vs 50.1% (HR 0.35, p<0.001). Despite this improvement in intracranial control, overall survival was not significantly different: 23.3 vs 28.7 months. Clinicians are weighing whether, in the context of CNS-active TKIs, delayed RT should become the default given the absence of a survival benefit from upfront cranial RT.
Discussed by: @HHorinouchi, @OncLive, @diegoadiazg
Divarasib + pembrolizumab produced an ORR of 72.9% and a median PFS of 19.3 months in first-line KRAS G12C-mutant NSCLC, with ORR of approximately 70% irrespective of PD-L1 expression, though driven primarily by the PD-L1 >50% subgroup, and no impact of KEAP1/STK11 co-mutations was observed. However, >70% Grade 3 treatment-related adverse events and 50% serious adverse events were reported. The debate is whether this chemo-free combination offers a viable frontline path despite the high-grade toxicity burden.
Discussed by: @Dr_Oncologista, @g_mountzios, @JordiRemon
Adjuvant nivolumab showed no improvement over observation: median DFS was 71.3 vs 68.8 months (HR 0.97, p=0.78), with no DFS benefit in PD-L1 ≥50% tumors (DFS HR 0.86; 95% CI 0.59–1.25), and no significant difference in OS. The result is characterized as strikingly inconsistent with neoadjuvant and perioperative chemo-IO studies, and oncologists are asking whether adjuvant IO failure reinforces neoadjuvant/perioperative chemo-IO as the mainstay in resectable NSCLC.
Discussed by: @HHorinouchi, @diegoadiazg, @StephenVLiu
Pralsetinib improved outcomes versus chemotherapy-based control in first-line RET fusion-positive NSCLC: mPFS 18.7 vs 9.0 months (HR 0.59; 95% CI 0.42–0.84; p=0.0027), ORR 65.5% vs 41.6%, and mDOR 20.6 vs 9.7 months. Grade ≥3 infections were markedly higher at 28.7% vs 9.6%, with fatal cases reported, and OS benefit was not observed, likely diluted by crossover. The discussion among specialists centers on whether the PFS benefit justifies the infection signal, particularly in the context of comparison with selpercatinib.
Discussed by: @HHorinouchi, @DrSanjayPopat, @StephenVLiu
Pumitamig + chemotherapy produced an ORR of 70.0% overall, with 71% in non-squamous and 74% in squamous NSCLC, with activity across all PD-L1 subgroups: 48% in PD-L1 <1%, 78% in PD-L1 1–49%, and 100% in PD-L1 ≥50%. Clinicians are asking whether dual PD-L1/VEGF-A blockade with pumitamig can outperform pembrolizumab + chemotherapy in a phase 3 setting.
Discussed by: @SuyogCancer, @HHorinouchi, @diegoadiazg
The sequential strategy of erlotinib + ramucirumab followed by osimertinib did not improve treatment-free survival versus upfront osimertinib: mTFS 16.6 vs 14.8 months (HR 1.03; p=0.49), with PFS of 14.9 vs 14.8 months (HR 1.08) and OS of 38.4 vs 44.0 months (HR 0.98). The sequential arm also had a higher treatment discontinuation rate of 36% vs 21%. This negative sequencing trial reinforces the question of whether upfront third-generation EGFR TKI remains the simplest best strategy in EGFR L858R NSCLC.
Discussed by: @M_Torasawa, @diegoadiazg, @StephenVLiu
ABBV-706 monotherapy at 1.8 mg/kg in the second-line setting produced an ORR of 82%, mPFS of 6.8 months, mDOR of 6.6 months, and mOS of 14.3 months; across the full monotherapy cohort ORR was 52% and mOS was 11.3 months. ABBV-706 in combination with the anti-PD-1 agent budigalimab yielded an ORR of 55% with mOS not reached. Oncologists are debating whether these data justify advancing ABBV-706 to larger trials as a new ADC option in heavily pretreated SCLC.
Discussed by: @RManochakian, @M_Torasawa, @LaurenByersMD
Ivonescimab + chemotherapy improved OS versus tislelizumab + chemotherapy in squamous NSCLC: mOS 27.9 vs 23.7 months (HR 0.66; 95% CI 0.50–0.87; p=0.0017), with 24-month OS of 64.7% vs 48.6% and OS benefit maintained in PD-L1 TPS <1% patients (HR 0.64); Grade ≥3 TRAEs were 69% vs 59% and G3+ bleeding occurred in only 3% vs 1%. The central debate is how generalizable a China-only trial with mostly male patients and weaker benefit in older patients will be, and whether HARMONi-3 will confirm these findings globally.
Discussed by: @HHorinouchi, @StephenVLiu, @diegoadiazg
In lorlatinib-naive patients, neladalkib produced an ORR of 46%, median PFS of 14.5 months, and DOR ≥12 months in 80%; in lorlatinib-experienced patients, ORR was 26%, median PFS 4.6 months, and median DOR 17.6 months with DOR ≥12 months in 54%. In the first-line setting, neladalkib yielded an RR of 86%, 91% DOR ≥12 months, and intracranial RR of 78%, with a reassuring safety profile (dose reduction 17%, discontinuation 5%). Clinicians are debating the role of neladalkib given FDA priority review and its activity in the post-lorlatinib setting, which represents the largest unmet need in ALK+ NSCLC.
Discussed by: @StephenVLiu, @OncLive, @diegoadiazg
In resected stage II–IIIA RET fusion-positive NSCLC, adjuvant selpercatinib reduced the risk of recurrence, progression, or death by 83% (HR 0.172; 95% CI 0.058–0.509; p=0.0003), with 2-year EFS of 91.5% vs 61.1% and mEFS NR vs 31.8 months; for stage IB–IIIA the HR was 0.16 with 2-year EFS of 94% vs 70%, and no deaths occurred on study treatment. The discussion among oncologists is whether adjuvant chemotherapy retains any role in RET+ early-stage NSCLC given an HR of 0.17, and how to ensure broad molecular testing to identify eligible patients.
Discussed by: @HHorinouchi, @RManochakian, @Dr_ElvinaA
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OBX-115, an engineered tumor-infiltrating lymphocyte therapy evaluated in the Agni-01 trial, achieved a 67% ORR and 93% DCR in PD-1-resistant metastatic melanoma (n=15), with 2 complete responses and a median duration of response not reached (range 1+ to 14+ months). The regimen uses tissue obtained by biopsy, outpatient low-dose lymphodepletion, and requires no IL-2. The central question is whether an IL-2-free, low-dose lymphodepletion approach can remove the principal toxicity barrier of cell therapy if the 67% ORR holds in phase 2.
Discussed by: @FunchainMD, @YGaritaonaindia, @Melanoma_doctor
SWOG S1609 DART enrolled 798 patients across 53 rare tumor cohorts at 1,083 US sites, with 24 of 53 cohorts (45%) demonstrating clear clinical activity and a median 3-year OS of 23% across these diseases. New data were presented for gestational trophoblastic neoplasia (biochemical ORR 75%) and basal cell carcinoma (ORR 29%, median PFS 10.6 months), alongside signals confirmed in refractory high-grade neuroendocrine carcinoma, angiosarcoma, and adrenocortical carcinoma. The interpretive challenge is how to weigh these positive signals given that many cohorts remain small, single-arm, and hypothesis-generating.
Discussed by: @OncoAlert, @PatelOncology
In the OptimUM-02 phase 2/3 trial in HLA-02:01-negative metastatic uveal melanoma, darovasertib plus crizotinib produced an ORR of 39.5% versus 1.9% for investigator's choice, with PFS of 6.9 versus 3.1 months (HR 0.42); high rates of toxicity were observed but with low rates of discontinuation. A separate analysis reported an ORR of 37% including several complete responses with this dual PKC/MET inhibition strategy. For HLA-A2-negative patients who cannot receive tebentafusp, clinicians are weighing whether systemic darovasertib-crizotinib outweighs local therapies, particularly in low-burden disease given its toxicity profile.
Discussed by: @FunchainMD, @OncoAlert, @OncLive
Anzu-cel, a PRAME-targeted TCR-T therapy, was evaluated in a phase 1b study (n=33) in PD-1-refractory cutaneous, uveal, and other melanoma, yielding an overall ORR of 64%, DCR of 91%, median duration of response of 14.6 months, and 12-month OS of 70%. By histology, ORR was 69% in uveal melanoma (median DoR 11 months) and 57% in cutaneous melanoma, with a separate analysis reporting cutaneous ORR of 50% and median DoR of 17 months. The debate centers on how PRAME-targeted TCR-T's HLA-restricted eligibility and higher CRS/ICANS risk should be weighed against modified TIL approaches in PD-1-refractory melanoma.
Discussed by: @Melanoma_doctor, @FunchainMD, @DrBetofMDPhD
The 5-year update of KEYNOTE-942 confirmed a 49% reduction in risk of recurrence or death with the personalized mRNA vaccine intismeran plus pembrolizumab versus pembrolizumab alone, with 5-year RFS of 72% vs 49% and 5-year OS of 92% vs 85%, alongside durable DMFS improvement and sustained T-cell clonotype expansion. Commentators noted encouraging TCR recruitment data while observing that no OS signal has emerged, consistent with all adjuvant trials to date. The core question is whether the sustained 5-year RFS and DMFS benefit justifies adopting personalized mRNA vaccines in resected melanoma before phase 3 OS data mature.
Discussed by: @ProfGLongMIA, @FunchainMD, @Dr_Oncologista, @Melanoma_doctor
NeoReNi II evaluated neoadjuvant nivolumab plus relatlimab in high-risk stage II melanoma (n=20), achieving a major pathological response rate of 65% and a complete pathological response rate of 60% at week 6, with 1-year OS of 100% in pCR patients and 67% in those with pathological non-response. No grade 4 or 5 toxicity was recorded, but significant endocrine toxicity occurred, including 35% hyperthyroidism and 10% adrenal toxicity. The question for clinicians is whether treating the primary lesion in place with neoadjuvant immunotherapy is feasible in high-risk stage II disease despite the risk of irreversible endocrinopathies.
Discussed by: @FunchainMD, @Dr_Oncologista, @Melanoma_doctor, @RonenStoff
The NeoINR trial evaluated two cycles of neoadjuvant relatlimab, nivolumab, and ipilimumab in clinical stage III resectable melanoma (n=22), yielding a pCR rate of 63.2% among those with macroscopic resectable disease and an MPR of 73%. One patient died from a treatment-related myocarditis, a toxicity signal that clinicians are weighing against the high pathologic response rate. The central debate is whether the pCR rate with triplet CTLA-4/PD-1/LAG-3 blockade justifies the toxicity profile, including a fatal myocarditis event, in this setting.
Discussed by: @CancerNetwrk, @FunchainMD, @Dr_Oncologista, @Melanoma_doctor
The RAMPART phase 2 single-arm trial evaluated definitive radiotherapy plus peri-RT cemiplimab in locally advanced, unresectable cutaneous squamous cell carcinoma, reporting an ORR of 65% and a 2-year event-free survival of 82%, described as comparable to outcomes in resectable disease. The open question is whether response-adapted radiotherapy combined with cemiplimab can consistently match resectable-disease outcomes in this unresectable population.
Discussed by: @FunchainMD, @DrBetofMDPhD, @Melanoma_doctor
The ADAM phase 3 trial evaluated 2 years of adjuvant avelumab versus placebo in Merkel cell carcinoma, showing 1-year RFS of 87% vs 70% and 2-year RFS of 79% vs 58% (HR 0.6, p=0.13), a result that did not reach statistical significance. The numerically notable difference alongside the non-significant p-value frames the debate over whether adjuvant avelumab has a clinical role in this rare disease.
Discussed by: @FunchainMD, @PGrivasMDPhD
The 3-year survival analysis of the phase 3 IGNYTE trial showed that RP1 plus nivolumab yielded deep and durable responses in advanced melanoma after progression on anti-PD-1 therapy, with a 45% 3-year OS in that refractory setting. RP1 was described as significantly and durably reducing tumor burden in at least 30% of patients without major toxicity, in a disease in which over 8,000 patients die of metastatic melanoma in the United States each year. The question is whether the 3-year IGNYTE survival data will support FDA reconsideration of RP1 for anti-PD-1-refractory melanoma patients who lack other options.
Discussed by: @CancerNetwrk, @MathewGWilson, @CureMelanoma, @Melanoma_doctor
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OPTIMA enrolled more than 4,400 patients with up to 9 positive lymph nodes, and in the ROR≤60 (low-risk) population, 5-year invasive breast cancer-free survival (IBCFS) was 94.8% with endocrine therapy alone versus 93.6% with chemotherapy plus endocrine therapy (HR 1.06; 90% CI 0.80–1.40), achieving non-inferiority (p=0.003) with an absolute difference of only 1.2%. Approximately 68% of clinically high-risk node-positive patients with a low ROR avoided chemotherapy while maintaining these outcomes. Piccart noted that for premenopausal patients with low GEP scores, the chemotherapy benefit observed in OPTIMA is largely attributable to chemotherapy-induced ovarian suppression. With only 4 years of median follow-up and no patients under 40 enrolled, debate persists over whether these data are sufficient to change practice for premenopausal node-positive patients, or whether the late recurrence pattern of ER+ disease demands 10-year follow-up.
Discussed by: @stolaney1, @JAMouabbi, @DrBarbiOnc, @ErikaHamilton9, @drsarahsam
Secondary safety data from DESTINY-Breast05 showed an ILD rate of 10%, including 2 fatal cases, with ILD rates higher in patients from Japan and in those with moderate renal impairment. Radiation pneumonitis incidence was approximately 30%; however, having prior ILD did not increase the risk of radiation pneumonitis, and no difference in ILD was observed based on whether radiotherapy was delivered sequentially or concurrently. The finding that prior ILD does not elevate radiation pneumonitis risk is central to the question of whether concurrent radiotherapy with adjuvant T-DXd can be supported.
Discussed by: @stolaney1, @ErikaHamilton9, @kazuki_nozawa
The phase III SAKK 96/12 REDUSE trial randomized 1,380 patients with bone-metastatic breast cancer or castration-resistant prostate cancer to denosumab 120 mg every 4 weeks or, after a 3-month loading phase, every 12 weeks. The every-12-week schedule was non-inferior for preventing symptomatic skeletal events (HR 1.02), with hypocalcemia rates of 30% versus 46% and fewer cases of osteonecrosis of the jaw. The reduced-frequency schedule also yielded approximately 50% lower cumulative denosumab exposure and approximately 53% reduction in drug costs per patient, prompting discussion of whether every-12-week dosing after a loading phase should become the new standard of care for bone metastases.
Discussed by: @ArmandOrlandi, @kazuki_nozawa, @ElisaAgostinett, @GaiaGriguolo
In SERENA-6, early ctDNA-guided switching to camizestrant produced a PFS HR of 0.45 with an absolute gain of 7.6 months, and PFS2 of 25.7 versus 19.1 months (HR 0.63; p=0.0037). Chemotherapy/ADC-free survival was 22.6 versus 18.7 months (HR 0.64), and OS HR was 0.87, continuing to mature. The ctDNA response was pronounced: a 99% median ctDNA drop by week 8 and clearance in 51% of camizestrant-treated patients versus 1.9% on aromatase inhibitor plus CDK4/6 inhibitor; in an exploratory analysis, ctDNA clearance was associated with an OS HR of 0.39. Clinicians debated how to interpret the PFS2 benefit in the absence of crossover in the control arm.
Discussed by: @DrRishabhOnco, @kazuki_nozawa, @JAMouabbi, @YAbdouMD
In the Neo-Healer trial, anbenitamab (a biparatopic HER2 antibody) plus albumin-bound docetaxel (HB1801) with or without carboplatin increased total pCR to 62.4% versus 51.2% in the ITT population (p=0.0036), and to 51.7% versus 44.4% in the ER+ subgroup, compared with THP with or without carboplatin. The trial enrolled a population that was 74% node-positive, 80% T2, 56% ER+, and 42% received carboplatin. A key methodological caveat noted is that the experimental arm used nab-docetaxel rather than conventional docetaxel, making it difficult to isolate the contribution of HER2 blockade, and the trial was conducted exclusively in China.
Discussed by: @stolaney1, @PTarantinoMD, @ElisaAgostinett, @Dr_Oncologista
An exploratory analysis of DESTINY-Breast09 showed that more than half of patients achieved complete response or deep partial response with first-line T-DXd plus pertuzumab, with 24-month PFS rates of 85% (CR) and 80% (deep PR). Among patients with PR less than 80% reduction, the 24-month PFS rate was 64%, and 36% for those with stable or progressive disease. Eighty percent of patients achieved maximal tumor reduction by 24 months, with responses continuing to deepen over time and no new safety signals observed. Whether these deepening responses argue against fixed-cycle stopping rules for this combination is an open clinical question.
Discussed by: @kazuki_nozawa, @DrRishabhOnco, @ErikaHamilton9, @Dr_Oncologista
In PANKU-Breast02, the EGFR×HER3 bispecific ADC izalontamab brengitecan (iza-bren) demonstrated PFS of 8.5 versus 3.1 months (HR 0.29; p<0.0001) and OS of 15.9 versus 12.5 months (HR 0.60; p=0.0019) compared with chemotherapy in pretreated metastatic TNBC, representing a 40% reduction in mortality risk and a median OS gain of 3.4 months. ORR was 51.7% versus 20.5%. Hematologic toxicity was substantial, with grade ≥3 thrombocytopenia in 52.7% and grade ≥3 anemia in 46.9% of patients in the iza-bren arm. Whether iza-bren can be validated globally and moved to earlier lines given this myelosuppression profile is under debate.
Discussed by: @ArmandOrlandi, @kazuki_nozawa, @PTarantinoMD, @Dr_Oncologista
The PATHWAY trial (n=184) comparing tamoxifen plus palbociclib versus tamoxifen plus placebo reported a median PFS of 24.4 versus 11.1 months (HR 0.59; p<0.001), with a particularly pronounced PFS benefit in premenopausal patients (HR 0.34). Median OS was 71.7 versus 62.0 months (HR 0.77; p=0.093), a result that did not reach statistical significance. The approximately 10-month OS difference sustains discussion around tamoxifen plus CDK4/6 inhibition as a viable endocrine backbone in the current CDK4/6 era.
Discussed by: @DrRishabhOnco, @stolaney1, @kazuki_nozawa, @Dr_Oncologista
In the lidERA trial, adjuvant giredestrant improved invasive disease-free survival across menopausal strata: in premenopausal patients (41% of the total population), the IDFS HR was 0.65 with a 3-year rate of 94.0% versus 91.5%, and in postmenopausal patients, HR 0.74 with a 3-year rate of 91.3% versus 88.3%; the ITT HR was 0.70 (3-year iDFS 92.4% vs 89.6%). Distant recurrence risk was also reduced, with HRs of 0.58 in premenopausal and 0.76 in postmenopausal patients. From a tolerability standpoint, 1.5% of premenopausal patients discontinued giredestrant due to musculoskeletal symptoms, compared with 5% who discontinued an aromatase inhibitor for the same reason. Clinicians are examining where adjuvant giredestrant fits relative to aromatase inhibitor plus CDK4/6 inhibitor combinations in high-risk ER+ early breast cancer.
Discussed by: @kazuki_nozawa, @Dr_ElvinaA, @stolaney1, @ErikaHamilton9
At approximately 84 months of follow-up, the final KEYNOTE-522 analysis confirmed 7-year EFS of 78.3% versus 69.8% (HR 0.68; 95% CI 0.54–0.86) and 7-year OS of 85.1% versus 77.2% (HR 0.64; 95% CI 0.49–0.85) with perioperative pembrolizumab added to neoadjuvant chemotherapy in high-risk early TNBC. EFS in patients achieving pCR was 90.4% versus 85.9% (HR 0.68), and in those with residual disease 57.6% versus 49.7% (HR 0.78). Adding perioperative pembrolizumab was estimated to prevent approximately 10% of recurrences and approximately 7% of deaths, at the cost of immune-mediated adverse events in 35% versus 13% of patients. With durable OS now confirmed, oncologists are debating how to refine the regimen—specifically how to test anthracycline omission and the role of adjuvant pembrolizumab in pCR patients.
Discussed by: @ArmandOrlandi, @stolaney1, @kazuki_nozawa, @PTarantinoMD
persevERA did not meet its primary endpoint: giredestrant plus palbociclib showed a numerical improvement in PFS versus letrozole plus palbociclib in first-line HR+/HER2− metastatic breast cancer (33.1 vs 28.2 months; HR 0.89) that did not reach the pre-specified threshold for statistical significance (p=0.155). The negative result, set against the PFS gains seen with oral SERDs in ESR1-mutant populations, has prompted clinicians to ask whether oral SERD benefit in the metastatic setting is anchored to ESR1 mutations rather than ET-sensitive first-line disease.
Discussed by: @YAbdouMD, @kazuki_nozawa, @BianchiniGP, @PTarantinoMD
A biomarker analysis of NATALEE in 3,022 patients showed that ribociclib plus a non-steroidal aromatase inhibitor provided consistent iDFS benefit across all PAM50 intrinsic subtypes in HR+/HER2− early breast cancer, with no significant interaction by subtype (interaction P=.34). The ITT iDFS HR was 0.71 and 0.72 in the biomarker population; by subtype, luminal A HR was 0.77 and luminal B HR was 0.71 (66% and 28% of the PAM50-profiled cohort, respectively). Higher genomic risk or proliferation scores trended toward greater ribociclib benefit, and higher CEACAM6 plus lower GATA3 expression were associated with increased benefit. The analysis raises the question of whether baseline gene expression can identify which HR+/HER2− patients derive the greatest adjuvant ribociclib benefit.
Discussed by: @stolaney1, @ErikaHamilton9, @kazuki_nozawa, @PTarantinoMD
SENOMAC reported 5-year OS of 94.4% with ALND omission versus 93.4% with completion ALND (HR 0.84), confirming non-inferiority (p<0.001), with a 5-year breast cancer-specific survival of 97.8% versus 97.3% at a median follow-up of 60 months. The morbidity difference was substantial: severe arm physical function problems occurred in 12.6% of patients who underwent completion ALND versus 3.6% in those who did not (p<0.001). Regional nodal irradiation was delivered in approximately 89% of patients, and clinicians are debating whether ALND can be safely omitted in the setting of 1–2 macrometastases without radiotherapy.
Discussed by: @ArmandOrlandi, @kazuki_nozawa, @DrRishabhOnco, @dr_yakupergun
In ASCENT-03, upfront sacituzumab govitecan (SG) yielded a PFS2 of 18.2 versus 14.0 months (HR 0.70) and a longer time to first subsequent therapy (11.2 vs 7.9 months) and time to second subsequent therapy (17.3 vs 16.6 months) despite 82% crossover to SG in the control arm. In ASCENT-04, PFS2 was not reached versus 21.0 months in the SG plus pembrolizumab versus chemotherapy plus pembrolizumab arms (HR 0.67), with a 24-month PFS2 rate of 63.7% versus 45.6%, despite 81% crossover to SG—representing a 33% reduction in the risk of a PFS2 event with the SG combination. SG benefit was consistent across Trop-2 expression quartiles, tumor BRCA wild-type and mutant subgroups, and HER2 IHC 0 and HER2-low subgroups. Given heavy crossover and the absence of a standardized PFS2 definition, the weighting of PFS2 as an endpoint for these trials is actively debated.
Discussed by: @DrRishabhOnco, @stolaney1, @ArmandOrlandi, @kazuki_nozawa
The PALMARES-2 real-world registry of 4,236 patients with HR+/HER2− metastatic breast cancer showed that approximately 20% continued endocrine therapy plus a CDK4/6 inhibitor beyond progression. Among those who did, median real-world PFS beyond progression was 10.5 months, and IPTW-weighted real-world OS was 69.4 versus 45.4 months (HR 0.51; p<0.001) compared with those who did not continue. Concomitant locoregional therapies were associated with improved outcomes in this analysis. The central clinical question is which HR+/HER2− patients—particularly those with oligoprogression—should continue this strategy beyond first progression.
Discussed by: @DrRishabhOnco, @kazuki_nozawa, @CateSposetti, @GaiaGriguolo
In VIKTORIA-1, gedatolisib plus palbociclib plus fulvestrant (triplet) produced a median PFS of 11.1 months versus 5.6 months with alpelisib plus fulvestrant (HR 0.50; p<0.0001), and the gedatolisib plus fulvestrant doublet yielded a median PFS of 11.3 months (HR 0.51) against the same comparator. ORR was 48.9% for the triplet and 35.7% for the doublet, compared with 26.0% in the alpelisib arm, with notably longer median duration of response in the gedatolisib arms. OS data remain immature but trend in favor of gedatolisib. The key trade-off is whether this doubling of PFS over an active alpelisib control justifies gedatolisib's weekly intravenous administration and stomatitis burden.
Discussed by: @DrRishabhOnco, @kazuki_nozawa, @PTarantinoMD, @SPremji7866
HER2CLIMB-05 subgroup data showed PFS prolongation with tucatinib maintenance across multiple clinically relevant subsets: brain metastases 8.5 versus 4.2 months (HR 0.64), HR+ disease 25.0 versus 18.1 months, and de novo metastatic disease 28.9 versus 16.8 months. The largest absolute benefit was observed in de novo metastatic HER2+ breast cancer (+12.1 months PFS). The magnitude of PFS difference by HR status and endocrine therapy use has prompted oncologists to examine how important continued endocrine therapy is in the HR+/HER2+ maintenance setting.
Discussed by: @tugbawitter, @Dr_ElvinaA, @YAbdouMD, @kazuki_nozawa
IRIS-A evaluated adjuvant capecitabine (1000 mg/m²) for 6 cycles plus trastuzumab for 1 year in 187 patients with stage IA HER2+ breast cancer, 87.2% of whom were HR-negative and 80% of whom had T1aN0 disease. With 66 months of follow-up, only 4 iDFS events occurred (2 locoregional, 2 contralateral; no distant events), yielding a 5-year iDFS of 97.8% and 5-year RFS of 98.9%. The question is whether this oral, IV chemotherapy-sparing regimen is a reasonable option for very small node-negative HER2+ tumors.
Discussed by: @ErikaHamilton9, @stolaney1, @Dr_ElvinaA
In evERA, giredestrant plus everolimus after CDK4/6 inhibitor progression produced a PFS2 of 19.0 versus 13.7 months (HR 0.69) and chemotherapy-free survival of 11.1 versus 7.9 months (HR 0.61). In the ESR1-mutant subgroup, chemotherapy-free survival was 12.6 versus 8.5 months (HR 0.46), and PFS2 was 19.0 versus 13.2 months (HR 0.69). Whether an oral SERD plus everolimus combination could serve as the preferred endocrine backbone after CDK4/6 progression—particularly in ESR1-mutant disease—is a central debate point.
Discussed by: @DrRishabhOnco, @ErikaHamilton9, @YAbdouMD, @Aydah_AlAwadhi
In 5,262 clinically node-positive patients enrolled in AXSANA/EUBREAST-03, axillary pCR rates varied markedly by tumor subtype: HR−/HER2+ 86%, HR+/HER2+ 71%, TNBC 68%, and HR+/HER2− 31%. The number of suspicious nodes at diagnosis—1–3 versus 4 or more—had no impact on axillary pCR rates (54.4% vs 53.6%; p=0.67). These data support a model in which tumor biology, rather than baseline nodal burden, should guide decisions around surgical de-escalation after neoadjuvant chemotherapy.
Discussed by: @DrRishabhOnco, @ArmandOrlandi, @ElisaAgostinett, @Dr_Oncologista
In HR+/HER2−, node-positive breast cancer with residual disease after neoadjuvant chemotherapy, adding non-cross-resistant adjuvant chemotherapy to endocrine therapy improved 10-year OS to 89.9% versus 82.9% (adjusted HR 0.56). The largest survival signal was in patients with residual node-positive disease (HR 0.47) and in those with Miller–Payne grade 3 response (HR 0.31). The benefit appeared strongest in residual node-positive patients, though the negative primary DDFS endpoint and small event count have prompted clinicians to weigh whether this strategy should be adopted broadly.
Discussed by: @ArmandOrlandi, @Lucarecco, @ElisaAgostinett
HELEN-Trio 011 showed that addition of camrelizumab to anthracycline-free neoadjuvant chemotherapy (6 cycles of docetaxel-carboplatin) significantly improved pCR rates in stage II–III TNBC, at 57.5% versus 45.4%. The pCR benefit was higher in PD-L1-positive patients; in PD-L1-negative patients a 9% difference was observed (p=0.165). Clinicians noted the result supports anthracycline-free chemoimmunotherapy designs such as SCARLET, which is ongoing in the United States.
Discussed by: @GaiaGriguolo, @DrSGraff, @to_be_elizabeth
AMBITION (JCOG1919E) enrolled 281 patients with HR+/HER2− metastatic breast cancer with no prior chemotherapy (approximately 30% de novo, approximately 60% with prior CDK4/6 inhibitor exposure) and randomized them to paclitaxel plus bevacizumab with or without atezolizumab. Adding atezolizumab did not significantly improve PFS (12.4 vs 11.2 months; HR 0.88; p=0.168) or OS (39.1 vs 31.2 months; HR 0.80; p=0.091), though a numerical OS improvement was observed. ORR was 73% versus 72%, with duration of response 12 versus 9.5 months. The OS signal despite a negative PFS endpoint sustains discussion about any role for immunotherapy in luminal advanced breast cancer.
Discussed by: @stolaney1, @ArmandOrlandi, @kazuki_nozawa
Updated TROPION-Breast02 data in first-line immunotherapy-ineligible metastatic TNBC showed Dato-DXd improved OS (HR 0.79) and PFS (HR 0.57) versus chemotherapy, with PFS2 of 15.6 versus 11.8 months (HR 0.61) and time to first subsequent therapy of 10.9 versus 5.6 months (HR 0.49). The favorable PFS2 trend suggests sustained benefit extending beyond initial progression and subsequent therapy. With both Dato-DXd and sacituzumab govitecan now demonstrating first-line PFS gains in immunotherapy-ineligible metastatic TNBC, clinicians are debating which TROP2 ADC should be preferred in this setting.
Discussed by: @ArmandOrlandi, @kazuki_nozawa, @GaiaGriguolo, @YAbdouMD
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Daraxonrasib is the first RAS-targeted therapy to demonstrate a clinically meaningful survival advantage over standard chemotherapy in previously treated metastatic pancreatic cancer, producing a median OS of 13.2 vs 6.6 months (HR 0.40, p<0.0001) and an ORR of 31.6% vs 11.2%; 53% of patients were alive at 12 months vs 19% with chemotherapy. The debate among oncologists centers on whether daraxonrasib should become the immediate second-line standard for RAS-mutant metastatic pancreatic cancer once approved, and how quickly access can expand.
Discussed by: @GIMedOnc, @CathyEngMD, @Dr_Oncologista, @jgong15
In unselected stage III colon cancer patients, aspirin 100 mg was not beneficial for DFS: 3-year DFS was 78.8% vs 75.4% (HR 0.84, p=0.0987) and 3-year OS was 95.2% vs 96.6% (HR 1.02). These results leave open whether adjuvant aspirin should be reserved for biomarker-selected subgroups such as PIK3CA mutants.
Discussed by: @CathyEngMD, @DaisukeKotani
In the 760-patient EMERALD-3 trial, STRIDE plus TACE improved PFS to 13.0 vs 9.8 months (HR 0.70, P=0.0007), with an OS trend of HR 0.84; the STRIDE plus lenvatinib plus TACE arm showed mPFS of 12.9 vs 8.1 months vs TACE alone, while OS was 39.5 vs 34.7 months (HR 0.84, 40% mature) for arm A vs C. Clinicians are debating whether the addition of lenvatinib to STRIDE plus TACE provides sufficient benefit to justify the additional toxicity in intermediate-stage HCC.
Discussed by: @jgong15, @graokane, @DrAngelaLamarca
Among patients with ctDNA clearance after 3 months, longer adjuvant chemotherapy did not appear to improve DFS; there was no benefit from continuing adjuvant chemotherapy if ctDNA was negative, and a rise in ctDNA at 3 months suggested no benefit to continuing beyond that point either. Oncologists are weighing whether ctDNA dynamics during adjuvant chemotherapy should now guide treatment duration rather than relying only on a single post-operative risk assessment.
Discussed by: @GIMedOnc, @CathyEngMD, @jgong15
In BREAKWATER Cohort 3, encorafenib plus cetuximab plus FOLFIRI improved PFS to 15.2 vs 8.3 months (HR 0.44) and OS to not reached vs 20.3 months (HR 0.53), with an ORR of 64.4% vs 39.2% compared with FOLFIRI ± bevacizumab. The availability of a FOLFIRI backbone has prompted discussion among clinicians about whether this triplet should be the preferred frontline regimen for BRAF V600E mCRC, particularly after oxaliplatin-associated neuropathy.
Discussed by: @CathyEngMD, @nataliagandur, @ParseghianC
Trastuzumab rezetecan produced a PFS of 5.5 vs 2.8 months (HR 0.33; 95% CI 0.21–0.53) and an ORR of 40.7% vs 4.5% vs standard of care in refractory HER2+ mCRC, with OS immature and grade ≥3 AEs predominantly hematologic; notably, only approximately 18% of patients had received prior anti-HER2 therapy. Specialists are questioning whether beating later-line standards such as TAS-102, regorafenib, or fruquintinib remains the relevant benchmark for HER2+ mCRC in this setting.
Discussed by: @MarioBalsaMD, @DraMartinezLago, @CathyEngMD
CIRCULATE demonstrated that ctDNA-positive patients had markedly worse outcomes — 3-year recurrence 19% vs 62% and 3-year DFS 77% vs 38% — yet the ITT primary endpoint was formally negative, in part because the ctDNA-positive rate was only 2.9% and the trial closed early due to loss of funding. Clinicians are debating whether these prognostic data support using ctDNA to guide adjuvant therapy decisions in stage II colon cancer despite the formal negative result.
Discussed by: @CathyEngMD, @GillSharlene, @FernandoOnco
IMbrave251 did not meet its primary OS endpoint: median OS was 14.6 vs 12.5 months (lenvatinib/sorafenib, mostly lenvatinib), with no significant difference between arms, and ORR of 7.5% vs 5.8%. Oncologists note the data may serve as a reference benchmark despite the negative result, and are debating whether adding atezolizumab to a TKI after progression on atezo-bevacizumab offers any advantage over TKI monotherapy.
Discussed by: @jgong15, @LorenzaRimassa, @EiocOncology
The PUMP trial showed no PFS benefit (15.0 vs 15.5 months), no hepatic PFS benefit (37.6 vs 21.5 months), and no OS benefit (HR 1.34, P=0.301) for adjuvant hepatic arterial infusion pump floxuridine after resection of low-risk colorectal liver metastases; a second source reports PFS of 15.0 vs 16.0 months with the primary endpoint not met. Clinicians are questioning whether this negative result closes the door on adjuvant HAIP in this low-risk population.
Discussed by: @DraMartinezLago, @graokane, @DrPraveenKammar
ATTRACTION-6 was a negative study: there was no significant difference in median OS (15.7 vs 15.8 months) or PFS (8.9 vs 7.7 months) in the ITT population for nivolumab plus ipilimumab plus chemotherapy vs chemotherapy alone, though a trend for better outcome in CPS >5 patients and an ORR of 57.9% vs 38.5% in favor of the chemo-IO arm were noted. The results have prompted oncologists to consider whether CPS-based patient selection should be reinforced for frontline immunotherapy combinations in gastric cancer.
Discussed by: @jgong15, @EiocOncology
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At a median follow-up of 42.8 months, enfortumab vedotin plus pembrolizumab sustained a median OS of 33.6 vs. 15.9 months (HR 0.53; 95% CI 0.45–0.63), with 3.5-year OS rates of 44.0% vs. 24.6%. Complete response rates doubled to 30.4% vs. 14.5%, and ORR reached 67.5% vs. 44.2%; landmark OS for the CR population is approximately 90%, with a median time to CR of 4.5 months. The central debate for clinicians is how to optimally duration and sequence EV plus pembrolizumab given that subsequent platinum-based chemotherapy yields a response rate of only 21% and a median OS of 11 months.
Discussed by: @tompowles1, @DrYukselUrun, @isamtavares
Talazoparib added to enzalutamide significantly prolonged rPFS in HRR-altered mCSPC (HR 0.48), with the strongest benefit in BRCAm patients (HR 0.37) and consistent activity in non-BRCAm patients (HR 0.57). The toxicity profile is substantial: grade ≥3 anemia occurred in 51% of patients and transfusions were required in 40%, while OS remains immature at an HR of 0.77. Clinicians are weighing which patients with HRR-altered mCSPC most warrant upfront PARP plus ARPI intensification given the cumulative burden of anemia and the risk of MDS/AML.
Discussed by: @DrChoueiri, @katy_beckermann, @SuyogCancer
The phase III SAKK 96/12 REDUSE trial randomized 1,380 patients with bone-metastatic breast cancer or castration-resistant prostate cancer to denosumab 120 mg every 4 weeks or, after a 3-month loading phase, every 12 weeks. The every-12-week schedule was non-inferior for preventing symptomatic skeletal events (HR 1.02) and produced lower rates of hypocalcemia (30% vs. 46%) and fewer cases of osteonecrosis of the jaw. The open question for oncologists is whether every-12-week denosumab should become the new standard given non-inferior skeletal protection alongside reduced toxicity and cost.
Discussed by: @ElisaAgostinett, @ArmandOrlandi, @kazuki_nozawa
The FDA approved durvalumab (Imfinzi) in combination with BCG for adult patients with BCG-naive, high-risk NMIBC, based on the POTOMAC phase III trial comparing BCG plus durvalumab vs. BCG alone; the combination reduced the risk of recurrence or death by 32%, with a DFS HR of 0.68 and 3-year metastasis-free DFS rates of 82% vs. 77%. Specialists note that OS and metastasis data indicate low cancer mortality in this population, and that checkpoint inhibitors carry approximately a 10% chance of serious side effects. The central debate is which BCG-naive high-risk NMIBC patients derive sufficient benefit to justify durvalumab intensification beyond optimized BCG.
Discussed by: @UroDocAsh, @OncBrothers, @tompowles1
In RAMPART, durvalumab plus tremelimumab versus active monitoring improved DFS with an HR of 0.65 (p=0.0004), while durvalumab alone versus active monitoring yielded an HR of 0.74 (p=0.041) without reaching a significant DFS benefit. In higher-risk disease, the combination showed a stronger signal (HR 0.52, p=0.0016), whereas durvalumab alone did not reach significance in that subgroup (HR 0.77, p=0.085). The trade-off clinicians are debating is whether the dual checkpoint DFS signal in higher-risk RCC justifies CTLA-4 addition given toxicity, immature OS data, and limited treatment completion.
Discussed by: @nataliagandur, @tompowles1, @GlopesMd
In 2,109 patients randomized in PROTEUS, perioperative ADT plus apalutamide improved pathologic response (8.9% vs. 1.0%) and 5-year metastasis-free survival (78.2% vs. 73.5%; HR 0.80), alongside improvements in EFS (HR 0.71), time to distant metastases (HR 0.68), and time to first subsequent therapy (median 74.2 vs. 41.5 months). Grade 3–4 adverse events were more frequent in the apalutamide arm, with rash as the principal driver. The debate for clinicians centers on whether these data change practice when overall survival remains immature and the control arm received perioperative ADT rather than surgery alone.
Discussed by: @nataliagandur, @DrRishabhOnco, @diegoadiazg
RADICAL did not improve its primary endpoint of SSE-free survival; median stratified SSE-FS was 17.9 vs. 17.6 months (stratified HR 1.24) and ORR was essentially identical at 22.2% vs. 22.9%. The trial closed early, with 98 patients enrolled, but OS was 28.3 vs. 19.7 months, numerically favoring the combination with late separation of curves. The debate is whether that numerical OS signal justifies further radiopharmaceutical study in RCC bone metastases despite the negative SSE-FS primary result.
Discussed by: @nataliagandur, @DrChoueiri, @yekeduz_emre
The phase II SURE-01 trial evaluated neoadjuvant sacituzumab govitecan before radical cystectomy in 44 patients with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy; after dose reduction to 7.5 mg/kg, the agent showed manageable toxicity and achieved a 29.5% overall ypT0N0-x rate, with greater activity in nonluminal tumors. The 24-month event-free survival rate was 71.4%, and a 29% pCR rate with monotherapy supports TROP2 as a reliable target, with biomarkers pointing to the payload TOP1 effect rather than the antibody target. Oncologists are debating whether this ~29% ypT0N0-x rate with single-agent sacituzumab govitecan establishes TROP2 as a viable neoadjuvant target for cisplatin-ineligible MIBC patients.
Discussed by: @AndreaNecchi, @nataliagandur, @isamtavares
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A pilot RCT in the HGSOC neoadjuvant chemotherapy setting randomized 41 patients to short-term fasting (36 hours before to 24 hours after chemotherapy; n=20) versus free diet (n=21), with 36 patients evaluable. The headline PFS signal showed mPFS 38 months with fasting versus 24 months with free diet (HR 0.26, log-rank p=0.045). The central debate is whether this 14-month absolute PFS improvement from a 36-patient fasting trial is credible, or whether it requires validation in a larger multicenter randomized trial before changing practice.
Discussed by: @LolaRNogueira, @SuyogCancer
DART combined ipilimumab plus nivolumab across 53 rare cancer cohorts, enrolling 798 patients across 1,083 US sites; 24 of 53 cohorts (45%) demonstrated clear clinical activity, and median 3-year overall survival reached 23%. New data in gestational trophoblastic neoplasia showed a biochemical ORR of 75%, while basal cell carcinoma demonstrated an ORR of 29% and mPFS of 10.6 months. The debate centers on which rare gynecologic histologies — including trophoblastic and clear cell ovarian — derive the most benefit from dual checkpoint blockade within this basket.
Discussed by: @MarioBalsaMD, @DrMirallas
Puxitatug samrutecan, a B7-H4-targeted antibody–drug conjugate, achieved a 47.1% ORR and a 7.2-month median PFS in advanced endometrial cancer. The question clinicians are debating is whether this B7-H4 ADC adds a viable new target for advanced endometrial and ovarian cancer.
Discussed by: @Dr_Oncologista, @womenofteal
In NRG-GY018, the pMMR OS HR is 0.86 (95% CI 0.69–1.08) at 81% information fraction — a signal driven in part by 81% of control patients receiving post-study ICI, with the HR drifting from 0.79 to 0.80 to 0.86 across successive data cuts. Benefit appears confined to patients with measurable disease (HR 0.76, 95% CI 0.58–0.98), with no signal and a trend against in nonmeasurable disease (HR 1.30, 95% CI 0.80–2.10). Serous histology emerges as a resistance driver across trials — RUBY pMMR serous HR 1.06 and DUO-E serous HR 1.46 — though RUBY TP53-mutant patients showed an HR of 0.55, suggesting that TP53 mutation alone does not account for the serous effect. Specialists are asking whether measurable disease status and histology should replace MMR status alone as the primary effect modifiers when selecting pMMR patients for ICI plus chemotherapy.
Discussed by: @DrBarbiOnc, @Dr_ElvinaA
Adding pembrolizumab to carboplatin and paclitaxel sustained an OS benefit versus placebo and chemotherapy in advanced/recurrent endometrial cancer in NRG-GY018, with a dMMR OS HR of 0.56 and a pMMR OS HR of 0.86. Notably, the OS benefit in the pMMR arm persisted despite 57% of patients in the control arm receiving immunotherapy as subsequent therapy, supporting its use as first-line treatment. The central question is how robust the pMMR OS signal is given heavy post-study ICI crossover in the control arm.
Discussed by: @drteplinsky, @TaroY_oncology, @EiocOncology
Relacorilant plus nab-paclitaxel significantly improved overall survival versus nab-paclitaxel alone in platinum-resistant ovarian cancer (16.0 vs 11.9 months, HR 0.65) at a median follow-up of 24.8 months, with no biomarker selection required. The OS benefit held in patients who received a taxane most recently (HR 0.67) and in those with a taxane-free interval of 6 months or less (HR 0.60). Clinicians are weighing whether the consistent benefit across taxane-exposure subgroups makes this combination a new standard irrespective of biomarkers.
Discussed by: @DrBarbiOnc, @EiocOncology, @CancerNetwrk
A phase II trial of abemaciclib plus hormonal therapy showed limited efficacy in HGSOC but benefit in LGSOC and ER-positive endometrial cancer. In ER-positive endometrial cancer, mPFS was 9 months (highest in the NSMP subgroup); in LGSOC, mPFS reached 17.5 months irrespective of KRAS status, with 28% of patients remaining on therapy for more than 3 years. The debate is whether these durable LGSOC responses justify routine CDK4/6 inhibition with hormonal therapy in hormone-driven gynecologic cancers.
Discussed by: @AlexisLeVee, @womenofteal
In a phase 1a study of IMA203CD8, a PRAME-directed CD4/CD8 T-cell therapy, 27 gynecologic cancer patients (24 ovarian cancer, 3 uterine cancer) were treated, with 89% confirmed responses observed. Across reporting, a confirmed ORR of 50% and several complete responses were noted in heavily pretreated ovarian and uterine cancers. Oncologists are debating whether PRAME-directed TCR-T cell therapy can translate this early activity into durable responses in platinum-resistant gynecologic malignancies.
Discussed by: @womenofteal, @ozdogan_md
The 4-year RUBY dMMR data show median PFS of 12.2 versus 7.7 months, a 0.28 reduction in hazard sustained over 4 years, and an 84% probability of being alive at 3 years. In the dMMR/MSI-H population, mPFS and mOS are both not reached, with a model-estimated cure fraction of 54% versus 14% for dostarlimab plus carboplatin/paclitaxel versus chemotherapy alone. Clinicians are asking whether this cure-fraction estimate supports dostarlimab plus chemotherapy as a curative-intent strategy in dMMR/MSI-H endometrial cancer.
Discussed by: @EiocOncology, @TaroY_oncology, @OncLearnNetwork
The randomized phase II CHRONO trial, comparing interval cytoreductive surgery after 3 versus 6 cycles of neoadjuvant chemotherapy in advanced high-grade epithelial ovarian cancer, did not demonstrate superiority for the 6-cycle approach with respect to DFS, OS, or perioperative outcomes and mortality. Surgery after 6 cycles was not superior to surgery after 3 cycles. Without a superiority signal at 6 cycles, the question clinicians face is whether 3 cycles of neoadjuvant chemotherapy before interval surgery should remain the default approach.
Discussed by: @CancerNetwrk, @EiocOncology, @womenofteal
MIROVA/AGO-OVAR 2.34, a randomized phase II trial of mirvetuximab soravtansine added to carboplatin-based therapy in FRα-high platinum-sensitive recurrent ovarian cancer, failed to show a PFS benefit: PFS was 9.79 versus 9.53 months (HR 1.00). A higher response rate did not translate into prolonged PFS. The debate is whether this miss confines mirvetuximab's role to the platinum-resistant setting, despite the observed response activity in FRα-high platinum-sensitive disease.
Discussed by: @womenofteal, @EiocOncology
TUB040, a NaPi2b-targeted ADC with an exatecan payload, showed a 67% ORR in a phase 1 dose-escalation trial (NAPISTAR 1-01). Clinicians are asking whether this early response rate positions TUB040 as a leading NaPi2b ADC option in platinum-resistant ovarian cancer.
Discussed by: @womenofteal, @DrBarbiOnc
The FDA approved relacorilant plus nab-paclitaxel for platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer after 1–3 prior regimens, based on phase 3 ROSELLA data showing improved PFS and OS versus chemotherapy alone. The PDUFA date is set for July 11. The practical question is how quickly this combination will enter routine clinic use for platinum-resistant disease.
Discussed by: @ClinOncNews, @DrBarbiOnc
In a phase 1 cervical cancer cohort, BAT8008 — a TROP2 ADC with exatecan payload — demonstrated a confirmed ORR of 26.5%, DCR of 77.9%, mPFS of 6.7 months, and mDoR of 9.0 months. CRB-701, a Nectin-4 ADC with MMAE payload, showed a confirmed ORR of 34.4%, mPFS of 4.3 months, and mDoR of 8.0 months at the 3.6 mg/kg dose level (n=32) in a phase 1/2 cervical cancer cohort. Oncologists are debating how these two agents will sequence against tisotumab vedotin in pretreated recurrent/metastatic cervical cancer.
Discussed by: @TaroY_oncology, @DrBarbiOnc
A phase 2 trial (TEDOVA) of the neo-epitope-based vaccine OSE2101 with or without pembrolizumab versus best supportive care in HLA-A2-positive platinum-sensitive ovarian cancer showed a PFS of 4.11 months for OSE2101 plus pembrolizumab versus 2.7 months for best supportive care. The question is whether this modest PFS difference justifies continued development of the vaccine approach in this setting.
Discussed by: @womenofteal, @OncLive
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