Efficacy and Feasibility of Neoadjuvant Osimertinib Demonstrated in Early-Stage EGFR+ Lung Adenocarcinoma

Neoadjuvant osimertinib (Tagrisso) is effective and feasible for use as treatment for patients with stage II-IIIB EGFR-mutant lung adenocarcinoma, according to interim analysis results of the NEOS study.

Across different cancer types, the efficacy of neoadjuvant therapy has been shown. The strategy has become more widely used to treat early-stage disease and to increase the potential for cancer downstaging and surgical resection to ultimately improve clinical outcomes overall.

In recent studies, investigators had provided evidence that first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) can be administered in the neoadjuvant setting and lead to clinically meaningful results for patients with EGFR-mutant non–small cell lung cancer. However, the data around third-generation EGFR TKis are limited and warrant further exploration of their abilities as neoadjuvant treatment.

NEOS is a Chinese prospective, multi-center, single-arm study (ChiCTR1800016948), which aims to determine the safety and efficacy of osimertinib as neoadjuvant therapy for the treatment of resectable EGFR-mutant lung adenocarcinoma, including in patients with deletion 19 (19del) and L858R mutations. The primary end point of the study was response rate and secondary end points included safety, R0 resection rate, quality of life, major pathologic response (MPR) rate, pathological complete response (pCR) rate, and N2 downstaging rate.

Patients enrolled in the study received osimertinib 80 mg orally daily for 6 six weeks followed by surgical resection. A total of 40 patients were included in the interim analysis for whom response to neoadjuvant therapy was performing according to RECIST v1.1.

Of the 40 patients enrolled, 34 were eligible to receive treatment. At baseline, the cohort had a median age of 63 years (range, 46-75), and was largely female (65%). The baseline ECOG performance score was 0 for 79% of the population and 1 for the remaining 21%. The most common clinical stage in patients at screening was stage IIIA (56%), however, a significant percentage of patients had stage IIB disease (24%), stage IIA disease (15%), or stage IIIB disease (6%). In terms of EGFR mutation type, most patients had 19del (59%), and 47% had an L858R mutation.

In 28 evaluable patients, the objective response rate observed in the study was 71%, all of which were partial responses. In addition, 29% of patients achieved stable disease for a disease control rate of 100%.

Twenty-two patients were considered for R0 resection following neoadjuvant therapy with osimertinib. Of those patients, 95% underwent R0 resection. The pathological downstaging rate in the population was 55%, and 40% of patients had N2 downstaging. Only 1 patient was shown to achieve a pCR.

According to the safety assessment, adverse events (AEs) were observed in 93% of the 28 evaluable patients. The most common AEs reported were rash (64%), oral ulceration (32%), and diarrhea (29%). There were no treatment discontinuation as a result of AEs reported in the study.

The NEOS study is ongoing in patients with stage II-IIIB EGFR-mutant lung adenocarcinoma receiving osimertinib in the neoadjuvant setting.

_References:

_{Lyu C, Fang W, Ma H, et al. Osimertinib as neoadjuvant treatment for resectable stage II-IIIB EGFR mutant lung adenocarcinoma (NEOS). J Clin Oncol. 2021;39 (suppl 15; abstr 8524). doi: 10.1200/JCO.2021.39.15_suppl.8524}