2021 Targeted Therapies of Lung Cancer (TTLC) Meeting - Posters-P06. The ASCENT Trial: A Phase II Study of Neoadjuvant/Adjuvant Afatinib, Chemoradiation +/- Surgery for Stage III EGFR-Mutant NSCLC

P06. The ASCENT Trial: A Phase II Study of Neoadjuvant/Adjuvant Afatinib, Chemoradiation +/- Surgery for Stage III EGFR-Mutant NSCLC - PDF

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The ASCENT Trial is a phase II study that examined the role of neoadjuvant and adjuvant afatinib, a tyrosine kinase inhibitor (TKI), in the treatment of stage III EGFR-mutant non-small cell lung cancer (NSCLC). The study enrolled patients with stage IIIA/B NSCLC who were eligible for curative-intent chemoradiation therapy and surgery. The primary outcome was the objective response rate (ORR) to neoadjuvant afatinib.<br /><br />Out of the 19 patients enrolled in the study, 11 of them (58%) achieved an ORR after receiving neoadjuvant afatinib. One patient who was initially deemed inoperable became a surgical candidate based on the response to neoadjuvant afatinib. However, two patients progressed on neoadjuvant afatinib or exhibited findings that clarified their presenting stage as stage IV, leading to their discontinuation from the study.<br /><br />The remaining 17 patients proceeded to chemoradiation therapy, and among the 10 patients who underwent resection, the major pathologic response (MPR) rate was 70%. Most patients (68%) started adjuvant afatinib after surgery or definitive chemoradiation therapy. Key grade 3/4 toxicities included rash, diarrhea, esophagitis, nausea, pneumonitis, and febrile neutropenia. There were no treatment-related deaths.<br /><br />With a median follow-up of 30.6 months, 47% of patients have experienced recurrence, with 5 of them having recurrence only in the central nervous system (CNS). The median progression-free survival (PFS) was 34.6 months, and the median overall survival (OS) was 69.1 months.<br /><br />The study concluded that neoadjuvant afatinib is associated with a favorable ORR and does not hinder the receipt of standard-of-care chemoradiotherapy and surgery in stage III EGFR-mutant NSCLC. The high rate of CNS-only recurrence suggests the potential for improved outcomes with more CNS-penetrant EGFR TKIs. These findings, along with the interim results of the ADAURA trial, support genotype-directed therapies in stage III EGFR-mutant NSCLC, although the optimal sequence of TKI therapy needs further definition.

Asset Subtitle

Andrew Piper-Vallillo

Meta Tag

Speaker Andrew Piper-Vallillo

Topic Stage III/Unresectable

Keywords

ASCENT Trial

neoadjuvant afatinib

EGFR-mutant NSCLC

chemoradiation therapy

surgery

major pathologic response

adjuvant afatinib

recurrence

progression-free survival

genotype-directed therapies