Tyrosine Kinase Inhibitor Therapy for Stage III EGFR-Mutated NSCLC
Posted: Thursday, March 4, 2021
To examine the role of tyrosine kinase inhibitor induction in patients with stage IIIA or B EGFR-mutated non–small cell lung cancer (NSCLC), Andrew Piper-Vallillo, MD, of the Massachusetts General Hospital, Boston, and colleagues conducted the phase II ASCENT trial of neoadjuvant and adjuvant afatinib in addition to standard-of-care curative-intent therapy. The final results were presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer Singapore (WCLC; Abstract FP01.05), held in virtual format in January 2021, support genotype-directed therapies in this patient population.
“Two months of neoadjuvant afatinib is associated with an objective response rate comparable to that seen in advanced disease and does not impair receipt of standard-of-care chemoradiotherapy with or without surgery,” the investigators commented. “The high rate of central nervous system (CNS)-only recurrence highlights a potential for improved outcomes with more CNS-penetrant EGFR tyrosine kinase inhibitors.”
A total of 19 patients received neoadjuvant afatinib; 17 underwent chemoradiotherapy with or without surgery. A dose reduction of afatinib was required in 26% of the study population. The objective response rate was 58% after neoadjuvant afatinib. Among the 10 patients who underwent lobectomy, the major pathologic response rate was 70%. More than half of patients (68%) started adjuvant afatinib after surgery or definitive chemoradiotherapy; Of them, four completed 2 years, three discontinued treatment early, two recurred during adjuvant afatinib, and four remain on adjuvant therapy. Rash, diarrhea, esophagitis, nausea, pneumonitis, and febrile neutropenia were the most commonly reported grade 3 and 4 toxicities; there were no treatment-related deaths.
At a median follow-up of 30.6 months, disease recurrence occurred in nine patients; of them, five experienced a CNS-alone recurrence. Disease recurrence occurred in three surgical patients. Of the patients who underwent definitive chemoradiotherapy, five experienced disease recurrence. The median duration of progression-free and overall survival were 34.6 and 69.1 months, respectively. After 2 years, the overall survival rate was 88%.
Disclosure: For full disclosures of the study authors, visit wclc2020.iaslc.org.
