Abstract CT217: 3-year update of neoadjuvant atezolizumab + chemotherapy in patients with resectable non-small cell lung cancer
Authors: Henick Brian S. , Gainor Justin F. , Awad Mark M. , Chiuzan Codruta , Izard Stephanie , Georgis Yohanna , Koch Peter D. , Garofano Robert F. , Wong Cheryl V. , Saqi Anjali , Grindheim Jessica M. , Schulze Katja , Rizvi Naiyer A. , Izar Benjamin , Taylor Alison M. , Shu Catherine A. 
Published: April 2023

Introduction: Neoadjuvant chemoimmunotherapy is promising in improving outcomes for patients with resectable lung cancer in the phase III setting, though data are immature at this time for overall survival (OS). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant immunotherapy + chemotherapy in this population.

Methods: This open-label, multi-center single-arm investigator-initiated phase II study was conducted at three hospitals in the USA. Neoadjuvant atezolizumab, carboplatin, and nab-paclitaxel were administered for up to 4 cycles prior to surgical resection. The primary endpoint of major pathologic response (MPR) has been previously reported; here we report mature disease-free survival (DFS) and OS as well as clinical characteristics of patients with recurrent brain metastases (BM) with integrated data from tumor genomics, gene expression, and quantitative immunofluorescent (QIF) measurement of immune markers.

Results: Of 30 enrolled patients, 29 were taken to the operating room with 26 completing successful R0 resection. 17 patients experienced MPR, of whom 10 had pathological complete response (pCR). The median follow-up time was 39.5 months (95% CI: 30.9-49.4). Median OS was 55.8 months (95% CI: 43.6-NA); median DFS was 34.5 months (95% CI: 18.4-NA). Landmark OS at 12, 24, and 36 months were 97%, 80%, and 77%, respectively; DFS: 80%, 60%, and 49%. Radiographic and pathologic measures of response, as well as baseline PD-L1 levels, did not statistically significantly associate with DFS or OS. The strongest trends were observed with pCR (OS: HR 0.22, 95% CI 0.03-1.83; DFS: HR 0.45, 95% CI 0.12-1.65). Percent decrease of radiographic response correlated inversely with percent pathological regression (Pearson correlation -0.44, 95% CI: -0.71—-0.08). Of 14 patients evaluable for site of recurrence, 6 developed BM. 5/6 patients with BM died, with median time to recurrence of 12.4 months (95% CI: 9.9-32.6) and time to death of 45.3 months (95% CI: 22.7-55.8). 3/6 patients who developed BM experienced MPR (2 achieved pCR). Radiographic response and PD-L1 level did not significantly associate with development of BM. Patients whose tumors had mutations in STK11 and KEAP1 did not experience statistically worse DFS/OS, though incidence of BM trended higher. Reduced copy number of STK11 and KEAP1, which both reside on chromosome 19p, was observed in about 1/3 of tumors. Deletion of either gene was significantly associated with worse pathologic response, lower levels of PD-L1+ cells by QIF, and BM.

Conclusions: Mature OS data reveal sustained clinical benefit of neoadjuvant chemoimmunotherapy with atezolizumab. Predictivity of radiographic and pathologic surrogates for survival was limited. Further study is warranted to establish the associations between STK11 and KEAP1 genomic alterations and key clinical outcomes in early-stage NSCLC.

Citation Format: Brian S. Henick, Justin F. Gainor, Mark M. Awad, Codruta Chiuzan, Stephanie Izard, Yohanna Georgis, Peter D. Koch, Robert F. Garofano, Cheryl V. Wong, Anjali Saqi, Jessica M. Grindheim, Katja Schulze, Naiyer A. Rizvi, Benjamin Izar, Alison M. Taylor, Catherine A. Shu. 3-year update of neoadjuvant atezolizumab + chemotherapy in patients with resectable non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT217.