Frontline Forum: Testing and Targeted Therapy in EGFR Exon20+ NSCLC

As part of a CancerNetwork^® Frontline Forum program, Alexander I. Spira, MD, PhD, FACP; Millie Das, MD; Joshua K. Sabari, MD; and Misako Nagasaka, MD, PhD, reviewed updates in the management of EGFR exon 20 non–small cell lung cancer (NSCLC), and how these findings may apply to clinical practice.

Spira, codirector of the Virginia Cancer Specialists Research Institute and director of the Thoracic and Phase I Program, and Das, a clinical associate professor of Medicine and Oncology at Stanford Health, led one part of the discussion regarding the evolution of molecular profiling and next-generation sequencing in the NSCLC space. Moreover, they spoke to clinical and non-clinical factors informing treatment decision-making in the second-line setting. Additionally, they reviewed data from the phase 1 CHRYSALIS trial (NCT02609776) assessing amivantamab as a treatment for patients with disease progression following chemotherapy.

According to data from the CHRYSALIS trial, amivantamab elicited an objective response rate of 40% (95% CI, 29%-51%), and a median duration of response of 11.1 months (95% CI, 6.9-not reached).¹ Additionally, the clinical benefit rate was 74% (95% CI, 63%-83%). Common any-grade adverse effects (AEs) in the study’s safety population that were associated with EGFR inhibition included rash (86%), paronychia (45%), stomatitis (21%), pruritus (17%), and diarrhea (12%).

Sabari, a thoracic medical oncologist at Perlmutter Cancer Center of NYU Langone Health, and Nagasaka, a thoracic oncologist at the University of California, Irvine, also discussed clinical updates in the EGFR exon 20 NSCLC population. They spoke about potential novel treatment options including mobocertinib (Exkivity), as well as potential next steps in research such as moving drugs to earlier lines of treatment and obtaining a better understanding of mechanisms of acquired resistance to treatment.

According to findings from a phase 1/2 trial (NCT02716116), mobocertinib produced an ORR of 28% (95% CI, 20%-37%) by independent-review committee assessment and 35% (95% CI, 26%-45%) per investigator assessment in a cohort of platinum-pretreated patients with EGFR exon 20 insertion mutations.² Common AEs reported in the trial included diarrhea and rash.

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References

1. Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study. J Clin Oncol. 2021;39(30):3391-3402. doi:10.1200/JCO.21.00662
2. Zhou C, Ramalingam SS, Kim TM, et al. Treatment outcomes and safety of mobocertinib in platinum-pretreated patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer: a phase 1/2 open-label nonrandomized clinical trial. JAMA Oncol. 2021;7(12):e214761. doi:10.1001/jamaoncol.2021.4761