Outcomes with neoadjuvant chemotherapy and/or osimertinib in patients with <i>EGFR-</i> mutant resectable non-small cell lung cancers.

Abstract

8052 Background: There are currently no EGFR -tyrosine kinase inhibitors approved for neoadjuvant treatment of resectable EGFR -mutant non-small cell lung cancers (NSCLC). The phase III multi-center trial NeoADAURA aims to evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in patients with resectable EGFR- mutant NSCLC. The primary endpoint of NeoADAURA is major pathologic response (MPR) rate. The statistical assumptions for the chemotherapy control arm were derived from the literature in NSCLC but not specific to an EGFR -mutant population. The true rates of pathologic response to neoadjuvant chemotherapy in patients with EGFR -mutant NSCLC are unknown. We report a multi-institutional analysis of surgical and pathologic outcomes in patients with resectable EGFR -mutant NSCLC treated with neoadjuvant therapies. Methods: This retrospective study evaluated patients at Memorial Sloan Kettering Cancer Center and Dana Farber Cancer Institute with stage II-IIIB N2 (AJCC v8) NSCLC with EGFR exon 19 deletions, exon 21 L858R mutations, or exon 18 G719X mutations who received neoadjuvant platinum-based doublet chemotherapy and/or neoadjuvant off-label osimertinib and underwent surgical resection with curative intent. Clinical characteristics, tumor next-generation sequencing results, R0 resection rate, pathologic complete response (pCR) rate, MPR rate, and downstaging rate were evaluated. Results: 51 patients with EGFR -mutant NSCLC met eligibility criteria and were treated with neoadjuvant osimertinib alone (N=23, 45.1%), platinum-based doublet chemotherapy alone (N=18, 35.3%), or osimertinib and platinum-based doublet chemotherapy (N=10, 19.6%). R0 resection rates were 91.3% with osimertinib, 72.2% with chemotherapy, and 90% with osimertinib and chemotherapy. Rates of pCR were 17.4% with osimertinib, 0% with chemotherapy, and 0% with osimertinib and chemotherapy. Rates of MPR were 43.5% with osimertinib, 0% with chemotherapy, and 10% with osimertinib and chemotherapy. Pathologic tumor downstaging occurred in 47.8% with osimertinib, 44.4% with chemotherapy, and 40% with osimertinib and chemotherapy; pathologic lymph node downstaging occurred in 34.8% with osimertinib, 27.8% with chemotherapy, and 40% with osimertinib and chemotherapy. Among the 4 patients with pCR, 3 had stage IIIA and 1 had stage IIIB adenocarcinomas at diagnosis; three had ex.19 deletions and 1 had an ex.21 L858R mutation. The most common co-occurring tumor genomic alterations were in TP53 (49%), CDKN2A/B (14%), and RB1 (10%). Conclusions: In this real-world multi-institution series, we did not observe pCR or MPR in patients with EGFR -mutant NSCLC treated with neoadjuvant chemotherapy. EGFR inhibitors may play an important role in the preoperative management of EGFR -mutant lung cancer.