Lung Cancer

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.

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Panelists discuss how the MARIPOSA trial (ASCO 2024) showed improved overall survival (OS) with amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant non–small cell lung cancer (NSCLC), supporting its FDA approval (October 2024). This regimen may become standard of care for select patients, but osimertinib with or without chemo remains vital. The complete response letter (CRL) for subcutaneous amivantamab may delay uptake.

Panelists discuss how osimertinib has been approved for patients with unresectable, EGFR-mutated stage III non–small cell lung cancer (NSCLC) following chemoradiation, based on the LAURA trial, which demonstrated a significant improvement in progression-free survival. In clinical practice, osimertinib is administered as consolidation therapy until disease progression or unacceptable toxicity. Ongoing studies like PACIFIC-9 and PACIFIC-8 are exploring the efficacy of combining durvalumab with other agents, potentially influencing future chemo-immunotherapy strategies in advanced NSCLC.

Panelists discuss how the MARIPOSA trial (ASCO 2024) showed improved overall survival (OS) with amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant non–small cell lung cancer (NSCLC), supporting its FDA approval (October 2024). This regimen may become standard of care for select patients, but osimertinib with or without chemo remains vital. The complete response letter (CRL) for subcutaneous amivantamab may delay uptake.

Panelists discuss how osimertinib has been approved for patients with unresectable, EGFR-mutated stage III non–small cell lung cancer (NSCLC) following chemoradiation, based on the LAURA trial, which demonstrated a significant improvement in progression-free survival. In clinical practice, osimertinib is administered as consolidation therapy until disease progression or unacceptable toxicity. Ongoing studies like PACIFIC-9 and PACIFIC-8 are exploring the efficacy of combining durvalumab with other agents, potentially influencing future chemo-immunotherapy strategies in advanced NSCLC.

The FDA granted orphan drug designation to rhenium (186Re) obisbemeda for the treatment of leptomeningeal metastases from lung cancer.

Panelists discuss how, in clinical practice, ADAURA (osimertinib) and ALINA (alectinib) are integrated based on EGFR/ALK status, stage, and recurrence risk. Adjuvant therapy duration is typically 3 years. Circulating tumor DNA (ctDNA), minimal residual disease (MRD) from ADAURA (ASCO 2024, Abs 8005) may refine treatment decisions by detecting MRD.

Panelists discuss how recent data from KEYNOTE-671, AEGEAN, and CheckMate 77T reinforce neoadjuvant therapy’s efficacy in early-stage non–small cell lung cancer (NSCLC), showing consistent survival benefits. In contrast, adjuvant data remain conflicting, limiting its role. Neoadjuvant therapy should be prioritized, with adjuvant therapy reserved for select high-risk patients.

Panelists discuss how emerging antibody-drug conjugate (ADC) data from TROPiCS-03 and IDeate-Lung01 suggest potential in extensive-stage small cell lung cancer (ES-SCLC), impacting sequencing with current therapies. T-cell engagers like BI 764532 and HPN328 may reshape treatment. MRI surveillance, per retrospective data and MAVERICK, offers an alternative to prophylactic cranial irradiation (PCI), though select factors may still justify PCI use.

Panelists discuss how the DeLLphi-301 trial demonstrated that tarlatamab, administered biweekly at a 10 mg dose, achieved a 40% objective response rate in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC). This led to its accelerated FDA approval in May 2024. Integrating tarlatamab into clinical practice may present challenges, including managing cytokine release syndrome and neurologic toxicities, as well as addressing financial considerations.

Panelists discuss how recent real-world data comparing atezolizumab and durvalumab in extensive-stage non–small cell lung cancer (ES-NSCLC) informs treatment selection, though direct comparisons remain limited. Lurbinectedin is a key second-line option, with emerging combination strategies.

Panelists discuss how the ADRIATIC regimen integrates immunotherapy post-chemoradiation in late-stage small cell lung cancer (LS-SCLC). In patients with paraneoplastic syndromes or immune disorders, immunotherapy requires caution. Prophylactic cranial irradiation (PCI) is considered for high-risk cases, while MRI surveillance is preferred for select patients to reduce neurotoxicity.

MT-8421, a novel engineered toxin body targeting CTLA-4, was not associated with grade 4 or 5 toxicities in patients with select advanced solid tumors.

Alberto Chiappori, MD, discusses the selection between frontline treatment options, including ensartinib, in ALK-positive non–small cell lung cancer.

Amivantamab plus lazertinib was approved in Canada for first-line EGFR-mutated locally advanced or metastatic non–small cell lung cancer.

Frontline treatment with datopotamab deruxtecan plus durvalumab with/without carboplatin proved active in advanced NSCLC without actionable alterations.

The Chinese NMPA has approved sacituzumab tirumotecan for EGFR-mutant advanced NSCLC following progression on an EGFR TKI and chemotherapy.

China’s NMPA has accepted an MAA seeking the approval of foritinib for ALK-positive advanced non–small cell lung cancer.