π¬ Lung/Head and Neck/Thymoma Intelligence Digest β Week 2026-W30
Sunvozertinib heads to the US for EGFR exon 20 NSCLC, two ADC readouts (sac-TMT and B7-H3 ris-rez) advance, dabrafenib-trametinib hits in RAI-refractory thyroid cancer, and multiple negative trials (ZEAL-1L, AdvanTIG-302, TREASURE) close doors.
β‘ TL;DR
π Publications
- Phase 3 Study of Niraparib-Plus-Pembrolizumab as Maintenance Therapy for Advanced/Metastatic Non-Small Cell Lung Cancer (ZEAL-1L). β Median PFS 5.55 months for both arms, HR 1.00
- AdvanTIG-302: Phase 3 Study of Ociperlimab (Anti-TIGIT) + Tislelizumab (Anti-PD-1) Versus Pembrolizumab in Untreated, Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer With PD-L1 β₯50. β Median OS 31.9 vs 29.4 months, HR 0.97; interim analysis terminated for futility
- Consolidative Thoracic Radiotherapy With Atezolizumab Maintenance in Extensive-Stage Small Cell Lung Cancer: The Phase 2 TREASURE Randomized Clinical Trial (AIO-TRK-0320). β Median OS 6.7 vs 13.4 months, HR 1.55; SAEs 61.3% vs 18.2%
π¦ Twitter / π¦ Bluesky
- Tumor suppressor genes and lineage plasticity in NSCLC β Loss of TP53 + RB1 creates the conditions for lineage transformation from adenocarcinoma to small-cell
- EGFR-mutant NSCLC transformed to small-cell: characterization and DLL3/B7-H3 targets β Characterization of EGFR mutant NSCLC transformed to SCLC (n=45); combo PFS 7.5m vs 2.8m; DLL3+ in 88%, B7-H3+ in 67%
- Sunvozertinib heads to the US via AstraZeneca-Dizal deal for EGFR exon 20 NSCLC β AstraZeneca reaches deal with Dizal to bring sunvozertinib to the US off phase 3 WU-KONG28 showing superiority over 1L chemo
- Systematic review: variable definitions of local control after lung SBRT β A systematic review reviewed 113 studies and found no consensus on the definition of local control
- Chemoimmunotherapy vs PD-(L)1 monotherapy meta-analysis in PD-L1-high NSCLC β Meta-analysis of 24 phase III trials (5,546 patients): OS HR 0.85, PFS HR 0.61 favoring chemoimmunotherapy in PD-L1 β₯50%
Full details below β
π What's Being Published
Phase 3 Study of Niraparib-Plus-Pembrolizumab as Maintenance Therapy for Advanced/Metastatic Non-Small Cell Lung Cancer (ZEAL-1L). β Ramalingam Suresh S et al., J Thorac Oncol
In the CR/PR population, the median PFS was 5.55 months for both the niraparib-plus-pembrolizumab arm (n=200) and the placebo-plus-pembrolizumab arm (n=201), with an HR of 1.00 (95% CI, 0.79β1.27; 1-sided p=0.502). No progression-free survival advantage was observed with the addition of niraparib, while hematologic toxicity was increased in the combination arm.
Clinical bottom line: Adding niraparib to pembrolizumab maintenance provides no PFS benefit and adds hematologic toxicity in advanced NSCLC.
AdvanTIG-302: Phase 3 Study of Ociperlimab (Anti-TIGIT) + Tislelizumab (Anti-PD-1) Versus Pembrolizumab in Untreated, Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer With PD-L1 β₯50. β Socinski Mark A et al., J Thorac Oncol
Median OS was 31.9 months (95% CI, 25.7βnot estimable) in Arm A (ociperlimab plus tislelizumab), 29.4 months (95% CI, 25.8β35.0) in Arm B, and 27.7 months (95% CI, 20.0βNE) in Arm C; the stratified HR for Arm A versus Arm B was 0.97 (95% CI: 0.76β1.23). The interim analysis was terminated for futility, with no OS improvement over pembrolizumab in PD-L1-high NSCLC.
Clinical bottom line: Adding anti-TIGIT ociperlimab to tislelizumab did not improve OS over pembrolizumab in PD-L1-high NSCLC, another failed TIGIT combination.
Impact of Prior Systemic Chemotherapy on Response to ROS1 Tyrosine Kinase Inhibitors in ROS1-Rearranged Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. β Kashizaki Fumihiro et al., JCO Precis Oncol
The pooled objective response rate was 79% (95% CI, 72 to 84) in TKI-naΓ―ve cohorts compared with 42% (95% CI, 32 to 51) in post-crizotinib cohorts, demonstrating a substantial attenuation of response following prior crizotinib exposure. This systematic review and meta-analysis quantifies the cost of delaying ROS1-directed therapy.
Clinical bottom line: Prior chemotherapy is associated with lower response to ROS1-TKIs, supporting early use of ROS1-directed therapy.
Genomic Landscape and Clinical Impact of MTAP Loss in Driver-Positive NSCLC: Insights from a Large-Scale Real-World Chinese Cohort. β Wei Qianhui et al., J Thorac Oncol
MTAP loss was identified in 10.4% of the overall cohort and was enriched in advanced-stage tumors harboring oncogenic drivers including EGFR mutations, ALK fusions, and MET and ERBB2 amplifications. Co-deletion with CDKN2A was highly prevalent in MTAP-loss tumors, occurring in 92.3% of cases.
Clinical bottom line: MTAP loss is a robust adverse prognostic biomarker in EGFR-mutant NSCLC treated with targeted therapy.
Consolidative Thoracic Radiotherapy With Atezolizumab Maintenance in Extensive-Stage Small Cell Lung Cancer: The Phase 2 TREASURE Randomized Clinical Trial (AIO-TRK-0320). β Bozorgmehr Farastuk et al., JAMA Oncol
Median OS in the combination arm was numerically shorter compared to atezolizumab alone (6.7 months [95% CI, 5.1β9.0] vs 13.4 months [95% CI, 10.7β17.5]; HR, 1.55 [95% CI, 0.90β2.69]; P=.34), while median PFS was similar (2.4 months [95% CI, 1.3β3.9] vs 2.6 months [95% CI, 1.2β3.9]; HR, 0.92 [95% CI, 0.54β1.55]; P=.85). Serious adverse events occurred in 61.3% vs 18.2% of patients, respectively.
Clinical bottom line: The published TREASURE trial confirms consolidative thoracic RT added to atezolizumab maintenance increases toxicity without survival benefit in unselected ES-SCLC.
Role of ctDNA Tumor Fraction in Selecting Immunotherapy Based Regimens in Advanced Non-small Cell Lung Cancer. β Dall'Olio Filippo G et al., Clin Cancer Res
In the CGDB Database (n=965), elevated ctDNA tumor fraction was prognostic for worse outcomes on ICBs and, when β₯5%, was predictive of benefit from ICB plus chemotherapy (HR for real-world progression-free survival 0.58 [0.41β0.82], p=0.002). These data position ctDNA tumor fraction as a candidate biomarker to guide regimen selection beyond PD-L1 in advanced NSCLC.
Clinical bottom line: High ctDNA tumor fraction identifies advanced NSCLC patients who derive greater benefit from chemo-immunotherapy.
BCL-2/BCL-xL inhibitor pelcitoclax with osimertinib for EGFR-mutated advanced non-small-cell lung cancer: a phase 1b trial. β Ma Yuxiang et al., J Immunother Cancer
The ORR was 10.7% and median progression-free survival was 2.7 months in patients who had previously progressed after third-generation TKI treatment plus chemotherapy (Cohort 1), compared with an ORR of 80.8% and mPFS of 16.4 months in TKI-naΓ―ve patients with or without prior chemotherapy (Cohort 3). The substantial difference in outcomes across cohorts reflects the impact of treatment history on the pelcitoclax-osimertinib combination.
Clinical bottom line: Pelcitoclax plus osimertinib showed activity in TKI-naΓ―ve EGFR-mutant NSCLC but limited benefit after prior third-generation TKI progression.
Clinical significance of EGFR amplification in patients with EGFR-mutated metastatic non-small cell lung cancer receiving first-line osimertinib. β Di Federico Alessandro et al., Clin Cancer Res
Patients with EGFR amplification treated with osimertinib achieved a similar objective response rate (88% vs 83%, p=0.23) but shorter median PFS (11.6 vs 19.0 months, HR 1.77, p<0.0001) and shorter overall survival (34.0 vs 40.1 months, HR 1.40, p=0.040) compared to those without amplification. EGFR amplification therefore identifies a subset with inferior outcomes despite comparable initial response.
Clinical bottom line: EGFR amplification correlates with distinct characteristics and worse outcomes on first-line osimertinib monotherapy in EGFR-mutated NSCLC.
Intratumoral Immune Heterogeneity Drives Divergent Outcomes to PD-(L)1 Blockade in Lung Cancer. β Cipriani Laura et al., Clin Cancer Res
Across cohorts, homogeneous immune-excluded (Hom-IE) tumors demonstrated longer OS compared to other groups: 34.6 vs 12.1β16.6 months in cohort A; 21.9 vs 8.4β13.3 months in cohort B; and 22.6 vs 11.3β13.4 months in cohort C. These findings position intratumoral immune heterogeneity, assessable from single samples, as a determinant of immunotherapy outcome independent of PD-L1 status.
Clinical bottom line: Intratumoral immune heterogeneity assessed from single samples identifies a microenvironment state linked to long-term immunotherapy benefit regardless of PD-L1 status.
Interstitial lung disease in patients treated with antibody-drug conjugates: a review. β Petrelli Fausto et al., Lung Cancer
ILD has been most extensively characterized with trastuzumab deruxtecan (T-DXd), for which pooled analyses report an incidence of approximately 10β15%, a median onset of 5β6 months, and a fatal-event rate of about 2.2%. The review frames ADC-related ILD as a class-relevant toxicity with implications for monitoring across agents.
Clinical bottom line: ADC-related ILD is a class-relevant toxicity requiring baseline risk assessment, serial imaging, and prompt intervention.
Brief Report: First-line Chemoimmunotherapy and Chemotherapy Outcomes in Patients with RET Fusion-Positive Lung Cancer in LIBRETTO-431. β Cui Can et al., J Thorac Oncol
The median PFS by blinded independent central review was 11.2 months (95% CI: 10.9β16.8) in chemoimmunotherapy-treated patients (n=83) and not reached (95% CI: 4.9βnot reached) in chemotherapy-treated patients (n=19); PFS was not significantly different between groups (p=0.8). The absence of an immunotherapy benefit in this RET fusion-positive cohort aligns with the known limited immunogenicity of this molecular subtype.
Clinical bottom line: In RET fusion-positive lung cancer, adding pembrolizumab to platinum-doublet chemotherapy did not improve outcomes; selective RET inhibitors remain preferred first-line.
Osimertinib Plus Gefitinib in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer and EGFR (C797X) Mutation Following First-Line Osimertinib: ORCHARD. β Goldberg Sarah B et al., Clin Cancer Res
Eight patients had a partial response, for a confirmed ORR of 26% (80% CI: 16β39); median duration of response was 4.2 months (95% CI: 2.8β5.5). Median PFS was 5.1 months and median OS was 19.0 months in this EGFR C797X post-osimertinib cohort.
Clinical bottom line: Osimertinib-gefitinib showed only modest benefit in EGFR C797X post-osimertinib and does not warrant further evaluation in this population.
Novel Immunotherapy Agents in Early-Phase Trials for Head and Neck Cancer. β Tan Harold Nathan et al., JAMA Netw Open
The overall response rate was 7.7% (12 patients) and the clinical benefit rate was 16.1% (25 patients) across early-phase trials in heavily pretreated HNSCC. Bispecific antibodies were associated with improved clinical benefit (odds ratio, 1.95; 95% CI, 1.23β4.15), whereas PIK3CA alterations were associated with reduced benefit (odds ratio, 0.03; 95% CI, 0.00β0.51).
Clinical bottom line: Novel immunotherapy agents show modest activity in heavily pretreated HNSCC, with bispecific antibodies the most encouraging class.
EMBER-Lung: Electronic Medical Record Boosting Molecular Testing in Early-Stage Non-Small Cell Lung Cancer. β Wang Willdragon et al., JCO Precis Oncol
The proportion of patients with comprehensive molecular testing increased from 36.9% (80/217) to 81.1% (197/243) with an EMR nudge intervention (P<.00001) across all stages (I to III). The intervention more than doubled testing rates in early-stage nonsquamous NSCLC after resection.
Clinical bottom line: An EMR-based nudge after resection more than doubled comprehensive molecular testing rates in early-stage nonsquamous NSCLC.
Durvalumab With Radiation Therapy in Patients With Inoperable Locally Advanced Non-Small Cell Lung Cancer Ineligible for Concurrent Chemoradiotherapy (DART). β Rimner Andreas et al., J Clin Oncol
The DART study met its primary endpoint with a 2-year PFS of 39% (one-sided CI, 29 to 100) and a 2-year OS of 54%. These results establish concurrent and consolidative durvalumab with radiation as an active approach for patients ineligible for concurrent chemoradiotherapy.
Clinical bottom line: Concurrent and consolidative durvalumab with radiation without chemotherapy is an active option for cCRT-ineligible locally advanced NSCLC patients.
Comparison of circulating tumor DNA assays for molecular residual disease detection in non-small cell lung cancer. β Cui Qian et al., J Thorac Oncol
At the landmark time point, the personalized assay achieved superior performance compared with tumor-naΓ―ve and tumor-informed assays, with a sensitivity of 40.9% (P=0.003), a specificity of 100.0% (P<0.001), a negative predictive value of 81.7% (P<0.001), and a positive predictive value of 100.0% (P<0.001). MRD positivity predicted shorter disease-free survival with an HR of 13.98.
Clinical bottom line: Tumor-informed personalized ctDNA assays optimize MRD detection and postoperative surveillance in stage IβIII lung cancer.
π£οΈ What People Were Discussing This Week
How these are chosen: filtered for clinical relevance, grouped by the new development discussed, then ordered by engagement (bookmarks and reposts).
Tumor suppressor genes and lineage plasticity in NSCLC
Loss of TP53 and RB1 creates the conditions for lineage transformation from adenocarcinoma to small-cell, with EGFR-TKIs selecting for pre-existing transformed clones rather than driving the transformation directly. STK11 loss produces an immune-cold tumor with reduced response to PD-1 monotherapy, while KEAP1 loss permanently activates the NRF2 pathway, enabling tumor cells to withstand oxidative and metabolic stress. The central question for clinicians is how knowledge of TP53, RB1, STK11, KEAP1, and SMARCA4 biology should shape routine testing strategies and resistance management in NSCLC.
Discussed by: @ChandrakanthMv, @ChandrakanthMv
EGFR-mutant NSCLC transformed to small-cell: characterization and DLL3/B7-H3 targets
A characterization study of EGFR-mutant NSCLC transformed to SCLC (n=45) showed a combination PFS of 7.5 months versus 2.8 months for EP-based regimens, though with acknowledged confounders. DLL3 expression was identified in 88% (and separately reported at 87.5%) of tumors, and B7-H3 was positive in 67%, positioning these antigens as potential targets β yet prior reports indicate poor response rates to tarlatamab in this setting, keeping the question of whether ADCs may offer a viable alternative open for debate.
Discussed by: @StephenVLiu, @Dr_Oncologista, @ChandrakanthMv
Sunvozertinib heads to the US via AstraZeneca-Dizal deal for EGFR exon 20 NSCLC
AstraZeneca reached a deal with Dizal to bring sunvozertinib to the US, a drug already approved for EGFR exon 20 NSCLC in China but previously unavailable to US patients. The deal follows phase 3 WU-KONG28 data showing superiority over first-line chemotherapy; WU-KONG1B data in the same indication reported an ORR of approximately 45% and a duration of response of approximately 13 months. Oncologists discussing this development directed attention to the gap between regulatory approval and patient access, asking how availability can be accelerated so exon 20 insertion patients are not left progressing during licensing negotiations.
Discussed by: @StephenVLiu, @mgonzalezvelMD, @christinemphmd, @Latinamd, @StephenVLiu
Systematic review: variable definitions of local control after lung SBRT
A new systematic review by Nourmohammadi et al., published in Radiotherapy & Oncology 2026, reviewed 113 studies and found no consensus on the definition of local control after lung SBRT. Despite the widely cited benchmark that local control exceeds 90%, the review demonstrates that this figure is entirely dependent on how individual studies define and measure the endpoint, making cross-study comparison unreliable. The central question is how the field should standardize the definition of local control to allow meaningful comparison of SBRT outcomes across institutions and trials.
Discussed by: @MedwatchKate, @jryckman3
Chemoimmunotherapy vs PD-(L)1 monotherapy meta-analysis in PD-L1-high NSCLC
A meta-analysis of 24 phase III trials enrolling 5,546 patients found superior outcomes with chemoimmunotherapy over PD-(L)1 monotherapy in advanced NSCLC with PD-L1 β₯50%: OS HR 0.85 and PFS HR 0.61 both favoring the combination. The authors state that their findings support prioritizing chemo-ICI over ICI alone in PD-L1-high NSCLC while prospective data are awaited. The debate among oncologists centers on whether these results shift practice now or whether individualized selection should be maintained pending prospective data such as from the INSIGNA trial.
Discussed by: @diegoadiazg, @NarjustFlorezMD
OptiTROP-Lung06: sac-TMT plus pembrolizumab beats chemo-pembro in PD-L1-negative NSCLC
The phase III OptiTROP-Lung06 trial met its primary endpoint, with first-line sacituzumab tirumotecan (sac-TMT, a TROP2 ADC) plus pembrolizumab achieving superior PFS over chemotherapy plus pembrolizumab in PD-L1-negative non-squamous NSCLC; an OS trend was also observed but did not reach significance. This is the first ADC plus IO phase III trial to demonstrate a positive result specifically in PD-L1-negative disease. Whether TROP2 ADCs plus immunotherapy will displace platinum chemotherapy in this population remains the central question, given that the OS benefit has so far only reached the level of a trend.
Discussed by: @StephenVLiu, @BalazsHalmosMD, @YGaritaonaindia
LIBRETTO-431 secondary analysis: chemoimmunotherapy no better than chemo alone in RET+ NSCLC
A secondary analysis of the phase 3 LIBRETTO-431 trial found no significant differences in PFS or OS between chemoimmunotherapy (n=83) and chemotherapy alone (n=19) in the control arm of RET fusion-positive NSCLC. In the chemoimmunotherapy group, median PFS by blinded independent central review was 11.2 months (95% CI: 10.9β16.8), while in chemotherapy-treated patients it was not reached (95% CI: 4.9βnot reached), with p=0.8. The findings reinforce that selective RET inhibition, not immunotherapy augmentation, is the relevant treatment axis in this molecular subtype, and raise the practical question of whether platinum-pemetrexed alone is adequate when a selective RET inhibitor is unavailable.
Discussed by: @StephenVLiu, @OncoAlert
CheckMate 227 vs 9LA real-world comparison in metastatic NSCLC
A retrospective real-world comparison from Japan (n=181) comparing nivolumab plus ipilimumab (CheckMate 227) versus nivolumab plus ipilimumab plus chemotherapy (CM9LA) found that adding two cycles of chemotherapy led to a higher response rate (68% vs 34%) and disease control rate (83% vs 53%), but no significant difference in PFS or OS, with higher grade 3 or greater treatment-related adverse events in the combination arm. Clinicians debated whether the superior response rate from adding chemotherapy to nivo/ipi justifies the added toxicity burden when survival outcomes remain unchanged.
Discussed by: @StephenVLiu, @OhioStatePIIO
Dabrafenib plus trametinib in BRAF V600E RAI-refractory differentiated thyroid cancer
Data from the dabrafenib plus trametinib versus placebo comparison in BRAF V600E radioiodine-refractory differentiated thyroid cancer showed a PFS of 12.8 versus 3.7 months (HR 0.38, p<0.0001) and an ORR of 57% versus 4%. Interim OS showed an HR of 0.66, which was not statistically significant. Specialists are weighing whether to prefer dabrafenib-trametinib over cabozantinib in previously treated patients with this molecular profile.
Discussed by: @OncoAlert, @DrRishabhOnco
AdvanTIG-302: another negative anti-TIGIT combination in PD-L1-high NSCLC
AdvanTIG-302, a randomized phase 3 trial of first-line ociperlimab (anti-TIGIT) plus tislelizumab versus pembrolizumab in PD-L1-high NSCLC, was terminated for futility. Median OS was 31.9 months versus 29.4 months with a stratified HR of 0.97 (95% CI: 0.76β1.23); response rates were 61% versus 49% and TRAEs occurred in 84% versus 79% of patients. After a string of failures across anti-TIGIT programs, the field is debating whether any path forward remains for this class in first-line NSCLC.
Discussed by: @StephenVLiu, @Socinski
ZEAL-1L: niraparib adds no benefit to pembrolizumab maintenance in NSCLC
The phase 3 ZEAL-1L trial, reported in J Thorac Oncol, randomized patients with advanced NSCLC who completed induction chemoimmunotherapy to pembrolizumab maintenance with either niraparib or placebo. Median PFS was 4.4 months in both arms per social media reporting of the trial, consistent with the published figure of 5.55 months for both arms (HR 1.00; 95% CI, 0.79β1.27; 1-sided p=0.502), with increased hematologic toxicity in the niraparib arm. The ZEAL-1L failure closes this particular combination strategy and prompts the question of whether PARP plus checkpoint maintenance in NSCLC retains any rationale.
Discussed by: @StephenVLiu, @OncogeneCancer
π₯ Top Ranked Tweets
OncoAlert @OncoAlert
RT @StephenVLiu: Phase III ELEVATE trial @NEJM for pts with resected stage IB to IIIB ALK+ NSCLC after adjuvant chemo randomized to ensartinib vs placebo x 2y (n=274). In stage II-III, 2y DFS 86.4% vs 53.5% (HR 0.20). Molecular testing for early stage NSCLC is critical!
https://t.co/6wQSu17deh
π 16 β€οΈ 58 π 20 π 3,721
OncoAlert @OncoAlert
Ensartinib in Resected ALK-Positive NonβSmall-Cell Lung Cancer
https://t.co/cZl3L8PjWM
In this phase 3 trial, 274 patients with completely resected ALK-positive stage IBβIIIB #NSCLC #LungCancer received ensartinib or placebo after adjuvant chemotherapy. Ensartinib π§ͺ significantly improved disease-free survival, reducing recurrence or death risk by 80%.
At 24 months, disease-free survival was 86β87% with ensartinib versus 53β57% with placebo. Grade β₯3 adverse events were more frequent with ensartinib, mainly rash. Overall survival data remain immature.
π¨ Pinging our incredible Lung Cancer Faculty!
@peters_solange
@christine_lovly
@GlopesMd
@DrSanjayPopat
@StephenVLiu
@HenningWillers
@HHorinouchi
@BRicciutiMD
@PercyLeeMD
@jillfeldman4
@bensolomon1
@Latinamd
@DrJNaidoo
@barlesi
@UOzkerim
@FernandoOnco
@DrMirallas
@VanitaNoronha
@NarjustFlorezMD
@MartinReck2
π 3 β€οΈ 18 π 8 π 1,349
Hidehito HORINOUCHI @HHorinouchi
π₯ELEVATE: Adjuvant ensartinib in resected ALK+ NSCLC
π @NEJM
βStage IB-IIIB ALK+ NSCLC post-resection & adjuvant chemo
π―24-mo DFS rate 86.4 vs 53.5% (HR 0.20, 95%CI
0.11 to 0.38) in stage II-IIIB; OS immature
π’NCT05341583
πDr. Dongsheng Yue
#LCSM @OncoAlert @Larvol @ALKPositiveinc
https://t.co/a8A6Nr3Cj2
π 3 β€οΈ 8 π 2 π 1,068
OncLive.com @OncLive
7-year CROWN data: lorlatinib's median PFS still not reached vs 9.1 months with crizotinib in first-line ALK+ NSCLC (HR, 0.19). Alice Shaw, MD, PhD, reports 55% of lorlatinib patients remain progression-free at year 7, with sustained CNS control.
Read the full analysis: https://t.co/qpZBwJUtSc
#ALKPositiveNSCLC #Lorlatinib #LungCancer
π 0 β€οΈ 5 π 6 π 726
Lung Cancers Today @Lung_Cancers
π« ICYMI: Divarasib showed βclinically meaningful and statistically significant improvementsβ in both PFS and OS in the Krascendo 1 trial, meeting its primary and key secondary end points.
β‘οΈ Learn more: https://t.co/aoMHqsC97q
#lcsm #KRAS #NSCLC #LungCancer https://t.co/2OYwOcP3xc
π 0 β€οΈ 0 π 0 π 84
Chris @Chris_Onc
#Perioperative NSCLC | Review | Nat Rev Clin Oncol
Neoadjuvant/perioperative chemo-IO is now standard for resectable non-oncogene-driven #NSCLC - but its success came from applying one uniform regimen across biologically heterogeneous tumors. This review reframes the question: not whether chemo-IO works, but how to decide who needs escalation, de-escalation, or could safely avoid unnecessary therapy.
Key messages:
πΉ pCR as the anchor. #pCR (0% residual viable tumor) is a robust, pan-trial surrogate for durable benefit β CheckMate 816 showed 5-yr OS >95% in pCR patients. It's the key anchor for adjuvant-phase escalation/de-escalation decisions. But ~30% pCR rates mean most patients don't achieve it.
πΉ Baseline biomarkers aren't enough alone. PD-L1 TPS β₯50% raises pCR likelihood (~40%), but no single baseline marker - PD-L1, TMB, TIL, clinical features - reliably guides escalation in isolation. The field needs dynamic, on-treatment readouts.
πΉ Dynamic biomarkers are the frontier. #ctDNA clearance, radiomics (AEGEAN-derived signatures predicted pCR at AUC 0.78), and metabolic imaging capture early response and complement pΠ‘R - but none is yet robust enough to replace pathology or guide de-escalation alone.
πΉ Intensifying for high-risk biology. For PD-L1-negative/immune-desert tumors where chemo-IO adds limited OS benefit, emerging strategies - TROP2 ADCs (Dato-DXd: pCR 35.2%, independent of PD-L1), PD-1ΓVEGF bispecifics (~30β44% pCR), novel ICI combos (LAG3, anti-CTLA4), mRNA vaccines, immune-sensitizing radiotherapy - aim to lift pCR and rescue insufficient responders.
The core tension is escalation vs. de-escalation timing - and whether surgery itself provides incremental benefit in every pCR patient, or mainly adds morbidity in some. The review's answer is a response-adaptive perioperative framework: baseline stratification β early on-treatment ctDNA/immune/radiomic dynamics β tailored local therapy (limited resection, consolidation radiotherapy, or switching systemic treatment) β pCR-guided adjuvant decisions (de-escalate if pCR; escalate/trial if residual disease).
Future direction: The recurring structural flaw is biomarker-agnostic trial design in unselected populations - effective agents keep failing to reach their optimal niche not from lack of efficacy, but from being tested in the wrong patients. The call to action: integrate dynamic imaging, ctDNA kinetics, and immune profiling into biomarker-enriched, adaptive trial designs - maximizing pCR in high-risk patients while sparing favorable-biology patients from overtreatment.
π 0 β€οΈ 0 π 0 π 6
The OncoAlert Network π¨ @oncoalert.bsky.social
Ensartinib in Resected ALK-Positive NonβSmall-Cell Lung Cancer
www.nejm.org/doi/full/10....
In this phase 3 trial, 274 patients with completely resected ALK-positive stage IBβIIIB #NSCLC #LungCancer received ensartinib or placebo after adjuvant chemotherapy. Ensartinib π§ͺ improved DFS
π 0 β€οΈ 0 π 0 π 0
Mustafa ΓzdoΔan, MD @ozdogan_md
π¨ On June 2025, the FDA granted accelerated approval to #DatoDXd β the first TROP2-directed ADC approved for this population.
β Why it matters:
β No standard options after osimertinib + chemo
β Immunotherapies underperform
β Historical ORR ~10β20%
β Dato-DXd: ORR ~45%, with durable responses (DOR 6.5 mo, OS 15.6 mo)
π Based on pooled analysis from TROPION-Lung01 & 05, this milestone fills a critical gap in later-line treatment for EGFRm NSCLC.
π§ EGFRm patients now live longer β but they still need smarter therapies when resistance inevitably emerges.
π Full visual summary π
#LungCancer #EGFR #NSCLC #ASCO #FDA @DaiichiSankyoUS @AstraZeneca #Oncology
π 8 β€οΈ 34 π 18 π 2,986
Dr. Estela Rodriguez @Latinamd
β¦βοΈHappy Monday! @FDAOncologyβ© grants accelerated approval to #DatoDxd datopotamab deruxtecan (Trop-2 ADC) for previously treated #EGFR+ NSCLC based on #TROPIONLung01, 05
β‘οΈORR of 42.7%, mDoR 7.0 mos
β‘οΈmOS 15.6 mos
β οΈAEs: Nausea, stomatitis, ILD https://t.co/37Samss8pz
π 0 β€οΈ 13 π 2 π 698
OncoAlert @OncoAlert
RT @OncoAlert: FDA πΊπΈgranted traditional approval to selpercatinib on July 14, 2026 for adult and pediatric patients (age 2+) with locally advanced or metastatic RET π§¬fusion-positive solid tumors that progressed after prior treatment or lack satisfactory alternatives.
https://t.co/R4L6whDiBP
Based on LIBRETTO-001 trial data across non-NSCLC, non-thyroid tumors (n=75), ORR was 47% with median DOR of 24.5 months #LungCancer
π¨ Pinging our Lung Cancer Faculty!
@peters_solange
@christine_lovly
@GlopesMd
@DrSanjayPopat
@StephenVLiu
@HenningWillers
@HHorinouchi
@BRicciutiMD
@PercyLeeMD
@jillfeldman4
@bensolomon1
@Latinamd
@DrJNaidoo
@barlesi
@UOzkerim
@FernandoOnco
@DrMirallas
@VanitaNoronha
@NarjustFlorezMD
@MartinReck2
π 0 β€οΈ 16 π 12 π 1,718
OncoAlert @OncoAlert
RT @DrRishabhOnco: π¨ A new biomarker-driven standard in thyroid cancer?
Phase III trial in previously treated BRAF V600E-positive, RAI-refractory differentiated thyroid cancer:
Dabrafenib + trametinib vs placebo
β PFS: 12.8 vs 3.7 months
HR 0.38, p<0.0001
β ORR: 57% vs 4%
β οΈ Interim OS: HR 0.66, not significant
Pyrexia: 48%
Serious AEs: 43% vs 25%
Take-home: A major PFS and response benefit after VEGFR-targeted therapy.
Verdict: Practice Changing
Would you choose this over cabozantinib?
@TheLancetOncol @oncoalert
#ThyroidCancer #PrecisionOncology
π 13 β€οΈ 50 π 20 π 3,795
OncoAlert @OncoAlert
FDA πΊπΈgranted traditional approval to selpercatinib on July 14, 2026 for adult and pediatric patients (age 2+) with locally advanced or metastatic RET π§¬fusion-positive solid tumors that progressed after prior treatment or lack satisfactory alternatives.
https://t.co/R4L6whDiBP
Based on LIBRETTO-001 trial data across non-NSCLC, non-thyroid tumors (n=75), ORR was 47% with median DOR of 24.5 months #LungCancer
π¨ Pinging our Lung Cancer Faculty!
@peters_solange
@christine_lovly
@GlopesMd
@DrSanjayPopat
@StephenVLiu
@HenningWillers
@HHorinouchi
@BRicciutiMD
@PercyLeeMD
@jillfeldman4
@bensolomon1
@Latinamd
@DrJNaidoo
@barlesi
@UOzkerim
@FernandoOnco
@DrMirallas
@VanitaNoronha
@NarjustFlorezMD
@MartinReck2
π 0 β€οΈ 16 π 12 π 1,718
OncoAlert @OncoAlert
RT @HHorinouchi: π₯ELEVATE: Adjuvant ensartinib in resected ALK+ NSCLC
π @NEJM
βStage IB-IIIB ALK+ NSCLC post-resection & adjuvant chemo
π―24-mo DFS rate 86.4 vs 53.5% (HR 0.20, 95%CI
0.11 to 0.38) in stage II-IIIB; OS immature
π’NCT05341583
πDr. Dongsheng Yue
#LCSM @OncoAlert @Larvol @ALKPositiveinc
https://t.co/a8A6Nr3Cj2
π 5 β€οΈ 15 π 7 π 2,172
Dr. Estela Rodriguez @Latinamd
RT @HHorinouchi: π₯ELEVATE: Adjuvant ensartinib in resected ALK+ NSCLC
π @NEJM
βStage IB-IIIB ALK+ NSCLC post-resection & adjuvant chemo
π―24-mo DFS rate 86.4 vs 53.5% (HR 0.20, 95%CI
0.11 to 0.38) in stage II-IIIB; OS immature
π’NCT05341583
πDr. Dongsheng Yue
#LCSM @OncoAlert @Larvol @ALKPositiveinc
https://t.co/a8A6Nr3Cj2
π 5 β€οΈ 15 π 7 π 2,172
OncoAlert @OncoAlert
RT @TejasPatilMD: βοΈVery important study in ES-SCLC. What is role of consolidation thoracic radiotherapy in ES-SCLC?
π³No benefit in PFS or OS with consolidation XRT vs atezo alone. Trial stopped early due to toxicity.
ππ½Given IMForte and potential DLL3 TCE maintenance options, careful pt selection needed for this approach.
@IyengarPuneeth @DrewMoghanaki @SclcSMASHERS @lcsmchat @OncoAlert
π 26 β€οΈ 53 π 16 π 7,967
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