Month in Review
March emphasized treatment optimization across multiple domains rather than a single practice-changing breakthrough. In advanced NSCLC, combination strategies in molecularly defined populations and novel agents in refractory disease showed signals of benefit, while real-world analyses suggested that sequencing of radiotherapy and immunotherapy may influence outcomes. In earlier-stage and locally advanced disease, perioperative immunotherapy and multimodal strategies continued to expand into more defined subgroups, with emerging phase II data informing clinical decision-making ahead of phase III evidence. At the same time, provocative findings in CNS-directed strategies challenge existing assumptions and highlight the importance of patient selection and treatment integration. Overall, the month reflects a shift toward more precise escalation, determining who benefits from intensification, and how best to deliver it.
Core Studies
Targeted Therapy
Aumolertinib With Carboplatin–Pemetrexed Versus Aumolertinib for NSCLC With EGFR and Concomitant Tumor Suppressor Gene Mutations (ACROSS2)
CA: A Cancer Journal for Clinicians
Study: Randomized phase III trial in EGFR-mutant NSCLC with co-occurring tumor suppressor gene alterations.
Key data: mPFS 19.78 vs 16.53 months; HR 0.58. Grade ≥3 AEs 25.9% vs 17.2%. OS immature.
Why it matters: Suggests benefit of combination therapy in biologically aggressive EGFR-mutant disease.
Clinical context & caveats: Selected molecular subgroup; increased toxicity; OS immature.
Immunotherapy
Gotistobart or Docetaxel in Metastatic Squamous NSCLC: Stage 1 of PRESERVE-003
Nature Medicine
Study: Randomized phase III (stage 1) in previously treated squamous NSCLC after PD-(L)1 inhibitor and platinum-based chemotherapy.
Key data: Median OS not reached vs 10.0 months; HR 0.46. ORR 20.0% vs 4.8%. Grade ≥3 TRAEs 42.2% vs 48.8%.
Why it matters: Demonstrates a strong signal in a setting with limited effective options.
Clinical context & caveats: Stage 1 analysis; requires confirmation in later phases.
Combination of Radiotherapy and Immunotherapy in Advanced Non–Small Cell Lung Cancer (OCEANUS)
JAMA Oncology
Study: Real-world cohort evaluating sequencing of radiotherapy and immunotherapy in advanced NSCLC.
Key data: Sequential vs concurrent iRT: median OS 20.3 vs 16.0 months; HR 0.68.
Why it matters: Suggests sequencing of RT and IO may impact outcomes.
Clinical context & caveats: Observational design; potential confounding by indication.
Early-Stage
A Subgroup Analysis of Perioperative Pembrolizumab in Clinical Stage II NSCLC From KEYNOTE-671
European Journal of Cardio-Thoracic Surgery
Study: Subgroup analysis of a randomized phase III perioperative trial in stage II NSCLC.
Key data: EFS HR 0.50; OS HR 0.69. pCR +21.3%; MPR +25.7%. R0 94.9% vs 86.4%.
Why it matters: Confirms benefit of perioperative immunotherapy in earlier-stage disease.
Clinical context & caveats: Subgroup analysis; OS immature.
Chemotherapy Combined With Immune Checkpoint Inhibitor for Operable Stage IIIA/B (N2) NSCLC (CHIO3 / AFT-46)
Lung Cancer
Study: Single-arm phase II in resectable stage III N2 NSCLC.
Key data: N2 clearance 73.3%. pCR 30%. mPR 50%. R0 93.3%. 18-month EFS 60.6%.
Why it matters: High nodal clearance and response rates in a challenging population.
Clinical context & caveats: Single-arm design; selection bias likely.
Multimodality
Long-Term Outcomes of Prophylactic Cranial Irradiation in High-Risk Metastatic NSCLC (PRoT-BM)
Radiotherapy & Oncology
Study: Randomized study evaluating PCI in metastatic NSCLC.
Key data: Brain metastases HR 0.40. Median OS 30.5 vs 19.2 months; HR 0.46.
Why it matters: Suggests potential survival benefit of CNS-directed prophylaxis.
Clinical context & caveats: Unexpected magnitude of effect; potential selection bias.
Other Notable Publications
Immunotherapy
Durvalumab Combined With Concurrent Chemoradiotherapy in Limited-Stage SCLC
Cancer
Study: Single-arm phase II.
Key data: Median OS 32.0 months. Median PFS 17.0 months. Grade ≥3 AEs 33.4%.
Why it matters: Adds prospective data in LS-SCLC.
Clinical context & caveats: Non-randomized; evolving treatment landscape.
Pembrolizumab With Platinum-Based Chemotherapy in NSCLC Patients With Untreated, Asymptomatic Brain Metastases (PHOEBS)
Cancer Research & Treatment
Study: Phase II single-arm.
Key data: Intracranial ORR 46.2%. Median icPFS 9.8 months. Median OS 10.7 months.
Why it matters: Supports systemic-first approach in selected brain metastasis patients.
Clinical context & caveats: Small sample size; underpowered.
Rare Subtypes
Tislelizumab Plus Anlotinib as First-Line Treatment in Pulmonary Sarcomatoid Carcinoma
Clinical Cancer Research
Study: Phase II single-arm.
Key data: ORR 55.2%. Median PFS 9.4 months. Median OS 14.4 months.
Why it matters: Encouraging activity in a rare and aggressive subtype.
Clinical context & caveats: Small cohort; non-randomized.
Radiotherapy
One Versus Three Fractions of SBRT for Peripheral Stage I–II NSCLC
International Journal of Radiation Oncology, Biology, Physics
Study: Randomized phase II.
Key data: No differences in local control, PFS, or OS. Grade ≥3 AEs 16% vs 12%.
Why it matters: Supports ultra-hypofractionated approaches.
Clinical context & caveats: Phase II; limited power.
Expert Takeaways
Combination strategies in molecularly defined populations are gaining traction, particularly in EGFR-mutant disease with high-risk features.
Novel agents in post-immunotherapy settings may begin to replace traditional chemotherapy options.
Perioperative immunotherapy continues to expand into earlier-stage disease with consistent signals across subgroups.
Integration of radiotherapy with systemic therapy remains an unresolved clinical question.
Notes on Generalizability & Bias Signals
Several studies rely on selected populations or subgroup analyses, limiting generalizability.
Observational data (OCEANUS) is subject to confounding by indication.
Single-arm phase II trials (CHIO3, PHOEBS) carry inherent selection bias.
Unexpected survival signals (PRoT-BM) require cautious interpretation.
Disclaimer: Publication dates refer to online-first publication.
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