📬 Lung/Head and Neck/Thymoma Intelligence Digest — Week 2026-W33

Jazz moves to withdraw lurbinectedin's 2L SCLC approval after LAGOON, SKYSCRAPER-03 adds a third negative TIGIT phase III in stage III NSCLC, and tarlatamab shows a 73% response rate in DLL3-high pulmonary carcinoid.

⚡ TL;DR

📄 Publications

SKYSCRAPER-03: A Phase III Study of Tiragolumab Plus Atezolizumab Versus Durvalumab in Locally Advanced, Unresectable, Stage III NSCLC After Platinum-Based Concurrent Chemoradiation. — Median IRF-assessed PFS in PD-L1+ patients was 19.4 months with tiragolumab plus atezolizumab versus 16.6 months with durvalumab (HR 0.96; 95% CI 0.75-1.23; p = 0.76)
Clinical Responses to Tarlatamab Among Patients with Pulmonary Carcinoid. — Response rate was 8/11 (73%) and disease control rate 11/11 (100%) in DLL3-high pulmonary carcinoid

🐦 Twitter / 🦋 Bluesky

Jazz moves to withdraw lurbinectedin's second-line SCLC approval after LAGOON misses OS, leaving clinicians to re-plan relapsed sequencing — Jazz plans to ask the FDA to withdraw lurbinectedin's approval in second-line small cell lung cancer based on the negative LAGOON phase 3 trial showing no OS benefit
Tarlatamab produces a 73% response rate in DLL3-high pulmonary carcinoid, extending the target beyond small-cell — Tarlatamab in DLL3-high pulmonary carcinoid gave 73% ORR and 100% DCR in n=11, with CRS in 82% and 22% grade 3
AXL inhibition preprint proposed as a way to overcome adaptive resistance to KRAS inhibitors in lung cancer — A new preprint reports that targeting AXL overcomes adaptive resistance to KRAS inhibition in KRAS-driven lung and pancreatic cancer
BRAF fusions emerge as an actionable NSCLC target, both de novo and acquired on EGFR therapy — A report describes BRAF fusions in NSCLC as both de novo and acquired, with acquired cases most frequently seen with EGFR drivers and one case responding to combined MEK and EGFR inhibition
SKYSCRAPER-03 published: tiragolumab plus atezolizumab fails against durvalumab after chemoradiation in stage III NSCLC — In stage III NSCLC after cCRT, PD-L1+ mPFS was 19.4 vs 16.6 months (HR 0.96, p=0.76) and all-comers 14.2 vs 13.8 months (HR 1.00), n=829

Full details below ↓

📄 What's Being Published

Manuscripts:

SKYSCRAPER-03: A Phase III Study of Tiragolumab Plus Atezolizumab Versus Durvalumab in Locally Advanced, Unresectable, Stage III NSCLC After Platinum-Based Concurrent Chemoradiation. — Wakelee H A et al., Ann Oncol

After a median follow-up of 33.0 months, median IRF-assessed PFS in PD-L1+ patients was 19.4 months with tiragolumab plus atezolizumab versus 16.6 months with durvalumab (stratified HR 0.96; 95% CI 0.75–1.23; p = 0.76); in PD-L1 all-comers, median PFS was 14.2 versus 13.8 months (stratified HR 1.00; 95% CI 0.84–1.19). Median OS in PD-L1 all-comers was 45.6 versus 45.8 months (stratified HR 0.98; 95% CI 0.80–1.20). The primary endpoint was not met, and the combination did not offer additional benefit over durvalumab.

Clinical bottom line: Consolidation durvalumab remains the standard after concurrent chemoradiation in stage III NSCLC, and anti-TIGIT added to PD-L1 blockade adds nothing in this setting.

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Clinical Responses to Tarlatamab Among Patients with Pulmonary Carcinoid. — Ross Jessica S et al., J Thorac Oncol

Among 11 patients with DLL3-high pulmonary carcinoid treated with tarlatamab at Memorial Sloan Kettering, the response rate was 8/11 (73%), including one patient with central nervous system-only disease, and the disease control rate was 11/11 (100%). Cytokine release syndrome occurred in cycle 1 in 9/11 (82%) patients, including 2 with grade 3 CRS.

Clinical bottom line: DLL3 is an actionable target beyond small-cell lung cancer, and tarlatamab deserves prospective testing in metastatic pulmonary carcinoid where systemic options are weak.

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🔗 Also discussed on social media →

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

Using pooled taletrectinib data from the TRUST-I and TRUST-II studies matched against published registrational data, taletrectinib was associated with significantly longer progression-free survival versus crizotinib (HR 0.48; 95% CI 0.27–0.88) and versus entrectinib (HR 0.42; 95% CI 0.27–0.65). Overall survival also favored taletrectinib 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 next-generation taletrectinib over crizotinib or entrectinib as first-line ROS1-directed therapy, though indirect comparisons cannot settle the question.

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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).

Jazz moves to withdraw lurbinectedin's second-line SCLC approval after LAGOON misses OS, leaving clinicians to re-plan relapsed sequencing

Jazz Pharma plans to ask the FDA to withdraw lurbinectedin's (Zepzelca) approval in second-line treatment of small-cell lung cancer, based on the negative LAGOON phase 3 trial that showed no OS benefit; the withdrawal does not affect lurbinectedin's first-line maintenance approval in combination with atezolizumab for extensive-stage SCLC. Clinicians are asking what to use after tarlatamab where clinical trials or tarlatamab are unavailable or not feasible, and whether payers will still cover lurbinectedin off-label. Some argue the FDA should retain lurbinectedin at second line on the grounds that not all patients can receive tarlatamab. With lurbinectedin's second-line indication going away, how are you sequencing relapsed SCLC after tarlatamab or when tarlatamab is not feasible?

Discussed by: @EladSharonMD, @OncoAlert, @NaglaAKarimMD, @DipeshUpretyMD, @pistoto2017, @TargetedOnc

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Tarlatamab produces a 73% response rate in DLL3-high pulmonary carcinoid, extending the target beyond small-cell

In 11 patients with DLL3-high pulmonary carcinoid, tarlatamab produced a 73% ORR and 100% DCR, with all patients experiencing reduction of their measurable disease and median progression-free survival not reached; CRS occurred in 82% of patients, with 22% grade 3, prompting debate over whether the higher CRS rate reflects tumor biology or the uniformly high DLL3 expression in this population. Separately, the DLL3-targeting antibody-drug conjugate zocilurtatug pelitecan received FDA orphan drug designation for the management of neuroendocrine carcinomas. Should DLL3-high metastatic pulmonary carcinoid now be enrolled prospectively onto tarlatamab trials, and how should the high early CRS rate be managed outside a trial?

Discussed by: @EladSharonMD, @OncLive, @OncLive

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AXL inhibition preprint proposed as a way to overcome adaptive resistance to KRAS inhibitors in lung cancer

A new preprint reports that targeting AXL overcomes adaptive resistance to KRAS inhibition in KRAS-driven lung cancer and pancreatic cancer, with the authors calling for KRAS inhibitor plus AXL inhibitor combination trials to sustain responses. In parallel, clinicians are debating the mechanistic difference between KRAS(OFF) and KRAS(ON) inhibitors and whether sequencing those agents is a route to overcoming resistance and restoring response. Is combining a KRAS inhibitor with an AXL inhibitor upfront the right way to blunt adaptive resistance, or does sequencing KRAS(OFF) and KRAS(ON) agents get there with less toxicity?

Discussed by: @OncoAlert, @OncLive

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BRAF fusions emerge as an actionable NSCLC target, both de novo and acquired on EGFR therapy

A report describes BRAF fusions in NSCLC occurring both de novo and as acquired alterations, with acquired cases most frequently seen with EGFR drivers; in one case, combined MEK and EGFR inhibition was effective. Over 60% of cases with de novo BRAF fusions did not have co-occurring drivers, and BRAF fusions are found across other tumor types with variable PFS and response rate on MEK inhibitor alone or combined with BRAF inhibitor, marking them as an emerging actionable target. Should RNA-based fusion testing at progression on EGFR therapy become routine so that acquired BRAF fusions can be targeted with MEK-based combinations?

Discussed by: @StephenVLiu, @SandraOrtizCua1

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SKYSCRAPER-03 published: tiragolumab plus atezolizumab fails against durvalumab after chemoradiation in stage III NSCLC

SKYSCRAPER-03 (n=829) reported in Annals of Oncology shows that tiragolumab plus atezolizumab did not improve outcomes over durvalumab after concurrent chemoradiotherapy in unresectable stage III NSCLC: PD-L1+ mPFS was 19.4 vs 16.6 months (HR 0.96, p=0.76), all-comers mPFS was 14.2 vs 13.8 months (HR 1.00), and mOS was 45.6 vs 45.8 months (HR 0.98), with the primary endpoint not met. Commentators note that biologic rationale alone was not sufficient, and a specific criticism raised is that TIGIT trials have selected patients by PD-L1 rather than TIGIT biology, with the argument that biomarker-blind IO should end. After three negative phase III TIGIT readouts, should any further anti-TIGIT development proceed without a TIGIT-based selection biomarker?

Discussed by: @HHorinouchi, @YGaritaonaindia, @Dr_Oncologista

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Perioperative toripalimab plus chemotherapy improves event-free survival in stage III resectable NSCLC, with a Chinese label expansion filed

Among patients with stage III resectable NSCLC, perioperative toripalimab plus platinum-based chemotherapy improved event-free survival versus chemotherapy alone, with a higher major pathological response rate and pathological complete response rate and a manageable safety profile. China's NMPA has accepted a supplemental application expanding toripalimab's perioperative NSCLC indication to stage II–III disease. Does another positive perioperative PD-1 readout in stage III NSCLC change anything for practices already using neoadjuvant chemoimmunotherapy, or is the open question still who can skip surgery or adjuvant treatment?

Discussed by: @JAMA_current, @OncLive

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Hypofractionated radiation for advanced head and neck cancer reported in the Red Journal

A novel use of hypofractionated radiation in head and neck cancers reported in the Red Journal shows outcomes in patients with advanced disease, while a parallel review examining radiotherapy combined with checkpoint inhibitors across metastatic, unresectable, and postoperative HNSCC concludes that answers may lie in biomarker-driven selection rather than layering on more drugs. Where does hypofractionated radiation fit for advanced head and neck cancer patients who cannot tolerate conventional chemoradiation schedules?

Discussed by: @ASTRO_org, @IjmioJournal

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Perioperative pembrolizumab in locally advanced head and neck cancer is cost-effective only above CPS 10

In locally advanced head and neck cancer, perioperative pembrolizumab was cost-effective only for patients with PD-L1 combined positive score greater than 10, supporting biomarker-stratified immunotherapy use. In KEYNOTE-689, postoperative radiotherapy delays were observed in 53.6% of the pembrolizumab arm and 65.2% of the control arm, adding a practical consideration to the debate over patient selection. Should perioperative pembrolizumab in resectable head and neck cancer be restricted to CPS >10, and how do postoperative radiotherapy delays factor into that decision?

Discussed by: @JAMAOto, @Jdcramer

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🔥 Top Ranked Tweets

Vivek Subbiah, MD @VivekSubbiah

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