Lung Cancer

The EMA’s CHMP recommended the approval of first-line tislelizumab plus chemotherapy for extensive-stage small cell lung cancer.

Panelists discuss how medical professionals consider continuing osimertinib with second-line and subsequent therapies based on disease progression, resistance mechanisms, and patient response. It may be combined with other agents or switched depending on clinical trials, biomarkers, and overall treatment goals to optimize outcomes.

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The EMA’s CHMP has recommended the approval of perioperative nivolumab plus chemotherapy in resectable PD-L1–positive non–small cell lung cancer.

Panelists discuss how treatment decisions for advanced non–small cell lung cancer (NSCLC) without actionable mutations depend on factors like PD-L1 status, histology (eg, squamous [SQ]), and biomarkers like STK11/KEAP1. Chemotherapy may be added based on individual patient factors, with promising advancements expected in 2025.

Panelists discuss how emerging data on novel HER2-targeted agents, including Beamion LUNG-1 (zongertinib) and SOHO-1 (BAY 2927088), show promise for advanced non–small cell lung cancer (NSCLC). Additionally, the eNRGy trial and FDA approval of zenocutuzumab for NRG1 fusion–positive non–small cell lung cancer (NSCLC) offers new treatment avenues. Patient selection will depend on genetic profiling and treatment efficacy.

Fulzerasib plus cetuximab elicited deep efficacy in patients with KRAS G12C–mutated NSCLC enrolled in the phase 2 KROCUS study.

Adagrasib plus pembrolizumab continued to show promising efficacy in patients with KRAS G12C–mutated NSCLC and PD-L1 TPS of 50% or higher.

Panelists discuss how treatment decisions for advanced non–small cell lung cancer (NSCLC) without actionable mutations depend on factors like PD-L1 status, histology (eg, squamous [SQ]), and biomarkers like STK11/KEAP1. Chemotherapy may be added based on individual patient factors, with promising advancements expected in 2025.

Panelists discuss how emerging data on novel HER2-targeted agents, including Beamion LUNG-1 (zongertinib) and SOHO-1 (BAY 2927088), show promise for advanced non–small cell lung cancer (NSCLC). Additionally, the eNRGy trial and FDA approval of zenocutuzumab for NRG1 fusion–positive non–small cell lung cancer (NSCLC) offers new treatment avenues. Patient selection will depend on genetic profiling and treatment efficacy

Amivantamab plus lazertinib provides long-term survival benefit over osimertinib in EGFR-mutated advanced non–small cell lung cancer.

Benjamin Herzberg, MD, highlights novel therapies in the KRAS-mutated NSCLC landscape and ongoing questions research is seeking to answer in this space.

Olvi-vec plus chemotherapy led to disease control in extensive-stage small cell lung cancer that was relapsed/refractory to platinum chemotherapy.

Benjamin Herzberg, MD, details research in KRAS G12C-mutated NSCLC with divarasib and how he currently selects between available therapies in this space.

A Type II variation application has been submitted to the EMA for the expanded approval of sugemalimab for unresectable stage III NSCLC.

Panelists discuss how medical professionals balance maximizing progression-free survival with preserving future treatment options by considering disease biology, resistance mechanisms, and patient factors. At first progression, the NCCN recommends continuing current therapy or switching to amivantamab with a platinum doublet, based on mutation status, prior response, toxicity, and patient preferences.

Panelists discuss how medical professionals use shared decision-making by aligning treatment options with patient values, discussing benefits, risks, and preferences. Patients often prioritize longest progression-free survival (PFS), lowest toxicity, and shortest infusion time. Collaborative discussions ensure personalized, evidence-based care.

Panelists discuss how the 5-year follow-up data from the CROWN trial support lorlatinib as a frontline treatment for ALK-positive non–small cell lung cancer NSCLC with brain metastasis. For frontline therapy, starting at full dose is preferred, adjusting if needed. Post progression, lorlatinib can be continued or combined with other agents. Biomarker testing for ROS1 is essential, with recent data (TRIDENT-1 trial) favoring lorlatinib for ROS1-positive central nervous system (CNS) involvement. Novel agents like taletrectinib and zidesamtinib from TRUST-I/II and ARROS-1 trials show promise in expanding treatment options for ROS1-positive NSCLC.

Panelists discuss how MARIPOSA-2 (Popat S, et al, ESMO 2024) and the September 2024 FDA approval of amivantamab plus chemo as a second-line option highlight advances in non–small cell lung cancer (NSCLC) treatment. Strategies involve sequencing with emerging therapies like HERTHENA-Lung01, addressing resistance, and central nervous system (CNS) metastases. The complete response letter (CRL) for HER3-DXd and the shift in biologics license application (BLA) status for Dato-DXd from TROPION-Lung05 (Lisberg A, et al, ASCO 2024) will shape clinical practices and resistance management moving forward.

Panelists discuss how the 5-year follow-up data from the CROWN trial support lorlatinib as a frontline treatment for ALK-positive non–small cell lung cancer NSCLC with brain metastasis. For frontline therapy, starting at full dose is preferred, adjusting if needed. Post progression, lorlatinib can be continued or combined with other agents. Biomarker testing for ROS1 is essential, with recent data (TRIDENT-1 trial) favoring lorlatinib for ROS1-positive central nervous system (CNS) involvement. Novel agents like taletrectinib and zidesamtinib from TRUST-I/II and ARROS-1 trials show promise in expanding treatment options for ROS1-positive NSCLC.

Panelists discuss how MARIPOSA-2 (Popat S, et al, ESMO 2024) and the September 2024 FDA approval of amivantamab plus chemo as a second-line option highlight advances in non–small cell lung cancer (NSCLC) treatment. Strategies involve sequencing with emerging therapies like HERTHENA-Lung01, addressing resistance, and central nervous system (CNS) metastases. The complete response letter (CRL) for HER3-DXd and the shift in biologics license application (BLA) status for Dato-DXd from TROPION-Lung05 (Lisberg A, et al, ASCO 2024) will shape clinical practices and resistance management moving forward.

Amanda Herrmann, MD, discusses findings from the TIME-TOX Lung study, which retrospectively assessed the time toxicity associated with lung cancer clinical trials.

The European Commission approved durvalumab for limited-stage small cell lung cancer without disease progression following chemoradiation.

Panelists discuss how disease-related factors like central nervous system (CNS) involvement or specific metastatic sites can guide treatment selection, favoring agents with CNS penetration or targeted efficacy. Mutational factors, such as TP53 comutations, may impact therapy response. Patient-related aspects, including age and comorbidities, influence tolerability and regimen choice.

Panelists discuss how, when discussing frontline regimens for EGFR-mutated non–small cell lung cancer (NSCLC), the NCCN-recommended options include osimertinib monotherapy for its targeted approach with lower toxicity; amivantamab/lazertinib combination for potentially deeper responses in specific mutations; and osimertinib with platinum-doublet chemotherapy for more aggressive disease requiring enhanced tumor control.