The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting featured a debate on the optimal treatment strategies for non-small cell lung cancer (NSCLC), specifically addressing the role of neoadjuvant therapy compared to surgery. Experts from leading institutions presented data and engaged in discussions regarding recent clinical trial updates and patient case studies.
Lorlatinib vs. Crizotinib in ALK-Positive NSCLC: The CROWN Trial
Dr. Faith Abodunrin presented data from the phase 3 CROWN trial, which evaluated lorlatinib versus crizotinib in patients with ALK-positive NSCLC. The trial demonstrated a median progression-free survival (PFS) that was not reached (95% CI, 64.2-NR) with lorlatinib at a median follow-up of 60.2 months, compared to 9.1 months (95% CI, 7.4-10.9) with crizotinib (HR, 0.19; 95% CI, 0.13-0.27). Grade 3/4 adverse events occurred in 77% of patients in the lorlatinib arm, with common AEs including hypertriglyceridemia (25%), weight increase (23%), and hypercholesterolemia (21%).
The discussion raised questions about the optimal sequencing of tyrosine kinase inhibitors (TKIs). Dr. Gupta questioned whether lorlatinib should be used as a first-line option, considering the potential loss of subsequent TKI options upon disease progression. Dr. Abodunrin argued for providing the best upfront treatment, while Dr. Herbst suggested comparing the toxicity profiles of lorlatinib and alectinib. Concerns were raised regarding the tolerability of lorlatinib, including potential weight gain and cognitive effects.
Amivantamab Plus Lazertinib in EGFR-Mutated NSCLC: The CHRYSALIS-2 Trial
Dr. Divya Myadam Gupta presented findings from cohort C of the phase 1 CHRYSALIS-2 trial, which assessed amivantamab plus lazertinib in patients with atypical EGFR mutations. The overall response rate was 52% (95% CI, 42%-62%), with a median duration of response of 14.1 months (95% CI, 9.5-26.2). The median PFS was 11.1 months (95% CI, 7.8-17.8). Common grade 3 or higher adverse events included rash (13%) and hypoalbuminemia (8%).
Challenges associated with amivantamab administration were discussed, including the time commitment required for infusions and monitoring. Despite the efficacy of the combination, the complexity of administration may limit its widespread adoption as a first-line treatment option compared to oral TKIs.
Neoadjuvant Therapy vs. Surgery: A Shifting Paradigm?
The debate culminated in a discussion on whether neoadjuvant therapy should replace surgery in NSCLC. Dr. Jyoti D. Patel argued for the superiority of neoadjuvant therapy, citing opportunities for in vivo assessment of treatment response, improved cure rates, and the potential for tailored adjuvant therapy based on pathological response. She emphasized the importance of moving beyond traditional dogma and embracing a more personalized approach to treatment.
Dr. Thawani presented a counterargument, particularly for patients with EGFR mutations where adjuvant targeted therapy remains a standard of care. Concerns were raised regarding the potential for treatment-related complications, such as pneumonitis, that could preclude subsequent surgery. The suitability of the CheckMate 816 regimen in patients with PD-L1-negative disease or oncogene-driven NSCLC was also questioned.
The debate highlighted the evolving landscape of NSCLC treatment and the need for ongoing research to optimize therapeutic strategies based on individual patient characteristics and disease biology.
