Non-Small Cell Lung Cancer (NSCLC)

Panelists discuss how overcoming resistance mechanisms in EGFR-mutated non–small cell lung cancer (NSCLC) remains a key unmet need, with future research focusing on targeting these mechanisms, exploring new drug combinations, and optimizing treatment sequences to improve patient outcomes.

The phase 3 HARMONi-6 trial found invonescimab plus chemotherapy improved PFS vs tislelizumab plus chemotherapy in squamous NSCLC.

In first-line, EGFR-mutated NSCLC, targeted therapies such as osimertinib or amivantamab plus lazertinib are recommended.

A 5-year follow-up of the phase 3 EMPOWER-Lung 1 showed the greatest survival benefits in patients with NSCLC who have a PD-L1 expression of 90% or more.

Pooled results from the TRUST-I and TRUST-II trials showed that taletrectinib led to infrequent neurological TEAEs in patients with ROS1-positive NSCLC.

Phase 3 CROWN trial findings suggest that patients with ALK-positive NSCLC may maintain efficacy even after reducing lorlatinib dosing to mitigate AEs.

A disease-free survival and minimal residual disease event-free status was maintained for most patients with adjuvant osimertinib for EGFR-mutant NSCLC.

Panelists discuss how the treatment landscape for EGFR-mutated lung cancer has evolved, with 3 strong options now available, including single-agent osimertinib and 2 combinations: osimertinib plus chemotherapy (FLAURA2) and amivantamab plus lazertinib (MARIPOSA), with the latter showing significant overall survival benefits.

Patients with ALK-positive NSCLC not vulnerable to neurological adverse effects or prone to weight issues, might benefit from treatment with lorlatinib.

Data from the phase 3 CheckMate 77T trial support the CHMP’s opinion on approving the perioperative nivolumab regimen for those with resectable NSCLC.

The “inescapability” of climate hazards may necessitate prioritization of research to improve outcomes among vulnerable populations who require treatment.

The safety profiles of osimertinib monotherapy and combination therapy were consistent with prior reports in EGFR-mutated non–small cell lung cancer.

Findings from the phase 3 CROWN trial evaluating lorlatinib in ALK-positive non–small cell lung cancer revealed a sustained PFS benefit with the agent.

Future work may focus on determining strategies for protecting the health of patients who undergo surgery during climate disasters.

Leticia Nogueira, PhD, MPH, highlights how facilities exposed to wildfires tend to have longer lengths of stay for patients undergoing surgery for NSCLC.

CAN-2409 plus valacyclovir or acyclovir elicited a median OS of 24.5 months in the overall population of patients who progressed after immune checkpoint inhibitor therapy.

A study assessed whether physicians would keep patients who received NSCLC surgery in the hospital longer as an improvisational strategy after wildfires.

In the phase 2 EMBRACE trial, ensartinib demonstrated an ORR of 53.3%, a DCR of 86.7%, and a tumor shrinkage rate of 33.3% in patients with METex14-positive NSCLC.

In patients who were pretreated and treatment naïve with RET fusion-positive NSCLC, selpercatinib yielded an ORR of 61.5% and 82.6%, respectively.

Future work may need to assess whether extended hospital stays improve surgical care outcomes during disasters, according to one of the study authors.

Retrospective data may offer actionable guidance for clinicians treating patients with non–small cell lung cancer and brain metastases.

Use of Deep-IO may help refine treatment precision and identify patients with advanced NSCLC who are likely to benefit from immune checkpoint inhibitors.

Multidisciplinary approaches, RNA-based next-generation sequencing, and patient-specific front-line treatment decisions are all important for curating effective NSCLC treatments.

Phase 2 data support further investigation of trastuzumab rezetecan as a treatment for patients with HER2-mutant non–small cell lung cancer.

Ivonescimab demonstrated a broad prolongation of PFS across various prespecified subgroups in patients with treatment-naïve, PD-L1–positive NSCLC.