📬 Lung/Head and Neck/Thymoma Intelligence Digest — Week 2026-W32

SKYSCRAPER-01 confirms anti-TIGIT failure in PD-L1-high NSCLC, the FDA approves zidesamtinib for ROS1-positive NSCLC and grants priority review to subcutaneous amivantamab in HNSCC, and long-term ICI beneficiaries in NSCLC are shown to die mostly of non-lung-cancer causes.

⚡ TL;DR

📄 Publications

SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1-High, Locally Advanced, Unresectable or Metastatic Non-Small Cell Lung Cancer. — Median INV-PFS 7.0 vs 5.6 months (HR 0.78)
Disease Kinetics and Practice Patterns in ≥4-Year Long-Term Beneficiaries of Immune Checkpoint Inhibitors for Advanced Non-small Cell Lung Cancer. — Of 3,144 patients, 537 (17%) survived ≥4 years and 295 (9.4%) were long-term beneficiaries
Tumor-infiltrating plasma cell profiling after PD-1 blockade reveals tumor-specific antibodies. — Resected NSCLC after neoadjuvant PD-1 blockade shows tertiary lymphoid structures with CD138+ plasma cells whose BCRs show somatic hypermutation and class switching

🐦 Twitter / 🦋 Bluesky

A new EGFR-mutant NSCLC review crystallizes the field's open dilemmas over combinations, biomarkers and toxicity — A review addresses biomarkers, rationalising options and challenging clinical scenarios in EGFR-mutant NSCLC
Four-year immunotherapy survivors in NSCLC die mostly of other causes, reframing long-term ICI care as survivorship — Long-term beneficiaries were 9.4% of 3144 patients, with lung cancer-specific OS 88% at 8 years and 68% of late deaths non-lung-cancer related
SKYSCRAPER-01 published: tiragolumab adds nothing to atezolizumab in PD-L1-high NSCLC, and clinicians ask whether anti-TIGIT biology was ever understood — In 521 patients, adding tiragolumab to atezolizumab did not significantly improve PFS (7m vs 5.6m, HR 0.78) or OS (23.1m vs 16.9m, HR 0.87)
Tumor-infiltrating plasma cells after neoadjuvant PD-1 blockade yield antibodies against citrullinated antigens and a working CAR construct — B cell receptors from neoadjuvant PD-1-treated NSCLC show somatic hypermutation and target citrullinated antigens on tumor cells
Adjuvant icotinib in resected stage IA EGFR-positive NSCLC reported with 100% three-year disease-free survival — In 128 patients with resected stage IA EGFR+ NSCLC, propensity-matched 3-year DFS was 100% with adjuvant icotinib versus 87% with observation

Full details below ↓

📄 What's Being Published

Manuscripts:

SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1-High, Locally Advanced, Unresectable or Metastatic Non-Small Cell Lung Cancer. — Peters Solange et al., J Clin Oncol

In this phase III trial (n=521), median investigator-assessed PFS was 7.0 months (95% CI, 5.6 to 9.8) with tiragolumab plus atezolizumab versus 5.6 months (95% CI, 4.4 to 7.0) with placebo plus atezolizumab (HR 0.78 [95% CI, 0.63 to 0.97]; P=.02 [nonsignificant]). Median OS was 23.1 months (95% CI, 17.7 to 28.8) versus 16.9 months (95% CI, 14.6 to 21.3) (HR 0.87 [95% CI, 0.7 to 1.1]; P=.22 [nonsignificant]), with grade 3–4 adverse events in 41.2% (n=110/267) versus 33.8% (n=89/263) of patients.

Clinical bottom line: Adding tiragolumab to atezolizumab misses both primary endpoints in PD-L1-high NSCLC, closing the book on this anti-TIGIT combination as first-line therapy.

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"SMAC"-down for the apoptosis-restoring drug, Xevinapant: What does its story reveal? — Jimenez-Labaig Pablo et al., Clin Cancer Res

In the Debio1143-201 phase II trial in locally advanced HNSCC, adding xevinapant to chemoradiation dramatically improved locoregional control and suggested favorable long-term survival. Unexpectedly, the TrilynX phase III trial was definitively negative, showing detrimental effects on survival and greater toxicity, which halted the development of SMAC mimetics as anticancer drugs.

Clinical bottom line: Xevinapant's collapse from a striking phase II signal to a harmful phase III result is a cautionary tale about relying on indirect peripheral-blood pharmacodynamic biomarkers for a narrow-therapeutic-index radiosensitizer.

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The genomic landscape and treatment outcomes associated with CDKN2A/MTAP loss in patients with non-small cell lung cancer. — Vokes Natalie I et al., Clin Cancer Res

CDKN2A/MTAP co-deletion (CMdel) occurred in 11.7% (n=1,991) of the primary dataset and 15% (n=1,676) of the validation dataset, enriched in mucinous histology, stage IV disease, and never-smokers. More than 50% of CMdel tumors harbored targetable co-alterations enriched in EGFR/ALK/RET and relatively depleted in KRAS. Time to next treatment did not differ by CM status for ICI-mono or TKI, but was shorter in CMdel for ICI-chemo and chemotherapy.

Clinical bottom line: CDKN2A/MTAP co-deletion marks a genomically distinct, immune-cold NSCLC subset with worse outcomes on chemo-containing regimens, and should be used to steer patients toward PRMT5/MAT2A inhibitor trials.

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Disease Kinetics and Practice Patterns in ≥4-Year Long-Term Beneficiaries of Immune Checkpoint Inhibitors for Advanced Non-small Cell Lung Cancer. — Torasawa Masahiro et al., J Thorac Oncol

Of 3,144 patients, 537 (17%) survived ≥4 years and 295 (9.4%) were long-term beneficiaries (median follow-up, 68.6 months); lung cancer-specific OS rates were 97.8% and 88.0% at 6 and 8 years, respectively. Late progression occurred in 26 patients (11.1%), all with ≤5 lesions and 84.6% with growth speeds ≤10 mm/month. Of 22 deaths ≥4 years post-ICI, only 7 (32%) were lung cancer-related, while 15 (68%) were from other causes, including secondary malignancies.

Clinical bottom line: Patients progression-free at 4 years on immunotherapy are functionally cured of lung cancer death but die of other causes, so their care should pivot to comprehensive survivorship and second-malignancy surveillance.

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Cancer risk and cause-specific mortality among people with thymoma in the United States. — Tao Jun et al., J Thorac Oncol

Among 3,051 individuals with thymoma, cancer risk overall was elevated (SIR=1.61, 95% CI=1.46–1.78), with site-specific elevations including lung (SIR=2.06, 95% CI=1.60–2.61), soft tissue including heart (SIR=5.46, 95% CI=2.36–11.0), urinary bladder (SIR=2.13, 95% CI=1.38–3.14), and thyroid (SIR=4.03, 95% CI=2.35–6.46). All-cause mortality was significantly elevated (SMR=2.86, 95% CI=2.70–3.04), with increases for deaths from cancer (SMR=6.17, 95% CI=5.67–6.70), infections (SMR=2.75, 95% CI=2.04–3.64), chronic obstructive pulmonary disease (SMR=1.92, 95% CI=1.39–2.58), and heart diseases (SMR=1.62, 95% CI=1.37–1.90). Compared with thymoma patients who did not receive a thymectomy, those undergoing partial or total thymectomy had lower overall mortality (MRR=0.44, 95% CI=0.37–0.51, and MRR=0.35, 95% CI=0.30–0.41, respectively).

Clinical bottom line: Thymoma survivors need lifelong second-cancer surveillance and infection prevention, and this SEER analysis supports thymectomy as associated with substantially lower mortality.

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Palliative Systemic Therapy in Advanced Thymic Epithelial Tumors in 2026-A Narrative Review. — Saalfeld Felix C et al., Cancers (Basel)

Platinum-based combination chemotherapy remains the standard first-line treatment for advanced thymic epithelial tumors. The review challenges the addition of anthracyclines to platinum in thymoma and critically appraises new combinations with antiangiogenic drugs and immune checkpoint inhibitors in thymic carcinoma, including their implications for therapy sequences.

Clinical bottom line: With evidence in thymic epithelial tumors limited to cross-trial comparisons of small non-randomized studies, the routine addition of anthracyclines to platinum in thymoma deserves to be questioned.

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Development and validation of a risk-stratification model for individualized management of leptomeningeal metastases in EGFR-mutant NSCLC (LM-Index). — Wu Yingxi et al., Lung Cancer

Multivariate analysis identified five independent predictors of poorer OS: ECOG PS ≥3, brain metastasis, meningeal enhancement on MRI, positive cerebrospinal fluid cytology, and intracranial pressure >220 mmH2O. The resulting risk score stratified patients into low-risk and high-risk groups with median OS of 22.6 months versus 9.9 months, respectively (p<0.001), and the model demonstrated good discrimination with a bias-corrected C-index of 0.73.

Clinical bottom line: The LM-Index turns five bedside variables into a validated survival stratification for EGFR-mutant NSCLC with leptomeningeal disease, giving clinicians a concrete tool for counselling and trial stratification.

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Tumor-infiltrating plasma cell profiling after PD-1 blockade reveals tumor-specific antibodies. — Meyerhoff R Ryan et al., Cancer Cell

In resected NSCLC after neoadjuvant PD-1 blockade, tumors orchestrate tertiary lymphoid structures with CD138+ plasma cells from which recombinant monoclonal antibodies were cloned using B cell receptors exhibiting somatic hypermutation and class switching. CAR T cells redirected with the scFv of the lead candidate antibody (PC-1) specifically targeted tumor cells and tumor-promoting myeloid cells in vivo without off-target activity.

Clinical bottom line: Tumor-infiltrating plasma cells in PD-1-treated NSCLC are a mineable source of tumor-specific antibodies against citrullinated antigens that can be converted directly into CAR constructs.

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Clinicopathological and prognostic validation of pulmonary carcinoid/NET G3: evidence for a distinct subgroup of well-differentiated neuroendocrine neoplasms. — Kirmann Jules et al., Lung Cancer

Among 155 pulmonary neuroendocrine neoplasms, eight (5.2%) fulfilled criteria for carcinoid/NET G3. These tumors exhibited well-differentiated morphology despite elevated proliferative activity, retained RB1 expression, and a wild-type p53 immunophenotype, distinguishing them from LCNEC, with an intermediate prognosis between conventional carcinoids and LCNEC.

Clinical bottom line: This single-center series independently validates the 2026 IASLC carcinoid/NET G3 category and argues for routinely integrating Ki-67, RB1, and p53 into pulmonary neuroendocrine diagnosis.

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Efficacy and safety of necitumumab and pembrolizumab combination therapy in advanced non-small-cell lung cancer with ≥50% PD-L1 expression: A nonrandomized phase II trial. — Horiike Atsushi et al., Clin Cancer Res

In 50 patients with PD-L1 ≥50% advanced NSCLC, the ORR was 76.0% (95% CI: 61.9–86.9; P<0.0001), with complete and partial response rates of 2.0% and 74.0%, respectively; median PFS was 15.7 months and median OS was not reached at the time of analysis. Grade 3 interstitial lung disease occurred in 5 patients (10.0%) and grade 5 cardiac arrest in 1 patient (2.0%).

Clinical bottom line: Necitumumab plus pembrolizumab yields a high response rate in PD-L1-high NSCLC, but a 10% rate of grade 3 interstitial lung disease means this combination cannot move forward without randomized safety data.

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Comparative efficacy of taletrectinib versus first-generation TKIs in TKI-naïve ROS1+ non-small cell lung cancer: A matching-adjusted indirect comparison. — Nagasaka Misako et al., Lung Cancer

After covariate adjustment, taletrectinib showed significantly longer PFS versus crizotinib (HR 0.48; 95% CI, 0.27–0.88) and versus entrectinib (HR 0.42; 95% CI, 0.27–0.65). OS was also significantly longer versus crizotinib (HR 0.34; 95% CI, 0.15–0.77) and versus entrectinib (HR 0.48; 95% CI, 0.27–0.88).

Clinical bottom line: In the absence of head-to-head trials, this matching-adjusted comparison supports taletrectinib over crizotinib or entrectinib as first-line ROS1 therapy — with the caveat that indirect comparisons cannot substitute for randomization.

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🗣️ 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).

A new EGFR-mutant NSCLC review crystallizes the field's open dilemmas over combinations, biomarkers and toxicity

A recently circulated review addresses biomarkers, rationalising options, and challenging clinical scenarios in EGFR-mutant NSCLC. Oncologists distilled the central tensions into five gaps: who really needs combination therapy, how to choose between frontline combinations, whether TKI monotherapy is still enough, how to reduce toxicity without sacrificing efficacy, and whether earlier treatment improves long-term outcomes. With both FLAURA2 and MARIPOSA now available, the practical question of how to choose between frontline EGFR regimens remains unresolved — the debate over which patients genuinely need an intensified frontline combination rather than TKI monotherapy remains active.

Discussed by: @DrYujiUehara, @maraantonoff, @herbloong

→ View representative tweet

Four-year immunotherapy survivors in NSCLC die mostly of other causes, reframing long-term ICI care as survivorship

Long-term beneficiaries comprised 9.4% of 3,144 patients, with lung cancer-specific OS of 88% at 8 years and 68% of late deaths attributable to non-lung-cancer causes; 85% of late progressors had growth rates ≤10 mm/month. The authors examined detailed clinical trajectories beyond 4 years — capturing insights that registries and large databases cannot easily provide — and framed the findings explicitly as a survivorship issue extending beyond cancer control. Patient advocates noted the significance of this framing, directing attention to the wider health and care needs of long-term responders. The open question is what routine follow-up for these patients should actually monitor if most deaths after four years on immunotherapy are not from lung cancer.

Discussed by: @M_Torasawa, @HHorinouchi, @lungcancereurope.bsky.social

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SKYSCRAPER-01 published: tiragolumab adds nothing to atezolizumab in PD-L1-high NSCLC, and clinicians ask whether anti-TIGIT biology was ever understood

In 521 patients, adding tiragolumab to atezolizumab did not significantly improve PFS (7m vs 5.6m, HR 0.78, 95% CI 0.63 to 0.97) or OS (23.1m vs 16.9m, HR 0.87 [95% CI 0.71 to 1.08], P=.22), despite promising phase II data. Commentators noted that TIGIT expression was neither prognostic nor predictive, and that patient selection was based on PD-L1 throughout — TIGIT itself never selected anyone, and when finally measured it predicted nothing. After Fc-active, Fc-enhanced, and Fc-silent anti-TIGIT antibodies have all failed in phase III, oncologists are debating whether any patient selection strategy remains worth testing.

Discussed by: @StephenVLiu, @YGaritaonaindia, @HHorinouchi

→ View representative tweet

Tumor-infiltrating plasma cells after neoadjuvant PD-1 blockade yield antibodies against citrullinated antigens and a working CAR construct

Tumor-infiltrating B cells from neoadjuvant PD-1-treated NSCLC harbor somatic hypermutated B cell receptors targeting citrullinated antigens on tumor cells, and the lead antibody-derived CAR T therapy — PC-1 CAR T — selectively targeted these cells in vivo without off-tumor toxicity, including tumor-promoting myeloid cells. Clinicians noted that intratumoral B cells and plasma cells are associated with improved response and asked whether B cell tumor-specific antibodies can be mined to develop focused CAR constructs. The central question is whether antibodies cloned from a patient's own tumor-infiltrating plasma cells can become a practical discovery pipeline for CAR constructs in NSCLC.

Discussed by: @HHorinouchi, @nataliagandur, @OncoAlert

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Adjuvant icotinib in resected stage IA EGFR-positive NSCLC reported with 100% three-year disease-free survival

A retrospective analysis in 128 patients with resected stage IA EGFR-positive NSCLC receiving adjuvant icotinib — a first-generation EGFR TKI used off-label — showed a propensity score-matched 3-year DFS of 100% with TKI versus 87% with observation, with no discontinuations for adverse events. Commentators observed that targeted therapies are expanding into the adjuvant and neoadjuvant settings for patients with oncogene-driven early-stage NSCLC, offering new opportunities to reduce recurrence risk. The debate centers on whether off-label adjuvant EGFR TKI is defensible in stage IA disease on the strength of a propensity-matched retrospective series alone.

Discussed by: @StephenVLiu, @OncLive

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Emi-Le shows a response signal in aggressive adenoid cystic carcinoma, a disease with no approved therapies

Interim phase 1 data show Emi-Le drove a 46.9% response rate, 1 complete response, and a 7.8-month median PFS in aggressive adenoid cystic carcinoma — a disease with no approved therapies. Investigators outlined the biologic rationale for and interim findings from the phase 1 study, and the central question for the field is whether a 46.9% response rate in aggressive adenoid cystic carcinoma is sufficient to justify accelerated development of a B7-H4 ADC in this orphan disease.

Discussed by: @OncLive, @OncLive

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🔥 Top Ranked Tweets

OncoAlert @OncoAlert

RT @FDAOncology: NEWS: @US_FDA approves a treatment for ROS1-positive non-small cell lung cancer.

https://t.co/rqaSYMhe45 https://t.co/NadHPYcKzp

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