Atezolizumab Following Neoadjuvant Atezolizumab and Resection Improves DFS in NSCLC

David P. Carbone, MD, PhD

Data for adjuvant atezolizumab (Tecentriq) following neoadjuvant atezolizumab and resection demonstrated an improvement in disease-free survival (DFS) and a trend toward improved overall survival (OS) in patients with resectable stage IB to IIIB non–small cell lung cancer (NSCLC) compared with those who did not receive adjuvant atezolizumab, according to updated findings from the phase 2 LCMC3 trial (NCT02927301).¹

Results presented at the 2023 European Lung Cancer Congress showed that in the major pathological response (MPR)–evaluable population (n = 137), those who received adjuvant atezolizumab (n = 53) experienced a 3-year landmark DFS rate of 83%, compared with 64% for those not given adjuvant atezolizumab (n = 84; HR, 0.44; 95% CI, 0.21-0.91).

At a median duration of follow-up of 3.1 years (range, 0.15-4.7) in the MPR-evaluable population, those administered adjuvant atezolizumab achieved a 3-year landmark OS rate of 89% compared with 77% for those not given adjuvant atezolizumab (HR, 0.48; 95% CI, 0.19-1.21).

“Neoadjuvant chemoimmunotherapy treatment without adjuvant treatment in the [phase 3] CheckMate 816 [trial (NCT02998528)] has shown to improve pathologic responses and event-free survival outcomes. However, it is completely unclear what the role of adjuvant immunotherapy is after neoadjuvant immunotherapy,” lead study author David P. Carbone, MD, PhD, said in a presentation of the data.

Carbone is a professor of internal medicine, the Barbara J. Bonner Chair in Lung Cancer Research, and the director of the James Thoracic Center at The James Ohio State Comprehensive Cancer Center in Columbus, Ohio.

Previously reported data from LCMC3 showed that the MPR rate, defined as 10% or less viable malignant tumor cells, was 20% (95% CI, 14%-28%) in 143 evaluable patients without EGFR or ALK alterations who had surgery, meeting the study’s primary end point.2 Additionally, the 3-year OS rate was 80%.

The open-label, single-arm trial enrolled patients with resectable, untreated, unselected stage IB to IIIA NSCLC, and select patients with stage IIIB NSCLC (n = 181). Patients underwent 2 cycles of neoadjuvant atezolizumab, and 159 patients proceeded to surgical resection. Adjuvant radiotherapy and/or chemotherapy, as well as 12 months of adjuvant atezolizumab, were optional following resection.

Among the 84 patients who did not receive adjuvant atezolizumab, 48 had no adjuvant treatment, and 36 received chemotherapy only. Of the 53 patients to get adjuvant atezolizumab, 36 were administered atezolizumab only, and 17 patients were treated with chemotherapy prior to atezolizumab.

Along with the primary end point of MPR, secondary end points included pathologic response and radiographic response by PD-L1, tumor mutational burden, neoantigen, and gene expression profiling. DFS and OS comprised exploratory end points.

Carbone noted that baseline characteristics were generally similar between patients who did and did not receive adjuvant atezolizumab. Notably, those administered adjuvant atezolizumab had a higher rate of squamous NSCLC (47% vs 31%), were more likely to have a PD-L1 tumor proportion score (TPS) of 50% or higher (40% vs 27%), and more likely to have MPR status (42% vs 8%).

Additional data showed that adjuvant atezolizumab also induced a benefit in the non-MPR population (n = 108). The 3-year landmark DFS rate was 80% in those given adjuvant atezolizumab vs 62% who did not receive it (HR, 0.48; 95% CI, 0.21-1.13). The 3-year landmark OS rate was 87% in patients who received adjuvant atezolizumab vs 75% in those who did not (HR, 0.50; 95% CI, 0.17-1.46).

In the MPR-evaluable population, the 3-year landmark DFS and OS rates in the entire population (n = 137) were 72% and 82%, respectively. Carbone noted that these rates were similar when accounting for stage. Those with stage I/II disease (n = 70) had a 3-year DFS rate of 75%, compared with 70% for patients with stage III disease (n = 67). The 3-year OS rates for these groups were 82% and 81%, respectively.

In a multivariable analysis for DFS, no significant difference was observed between patients with a PD-L1 TPS of at least 1% vs those with a PD-L1 TPS of less than 1% (TABLE).

“Impressively, the adjuvant atezolizumab vs no adjuvant [atezolizumab] and chemo vs no chemo subgroups in this population came out very strong in the multivariable analysis [for DFS],” Carbone said.

Regarding safety, any-grade adverse effects (AEs) were reported in 96% of patients, including 40% of patients who had a grade 3/4 AE and 5% of patients who experienced a grade 5 AE. Treatment-related AEs (TRAEs) of any grade were reported in 63% of patients, and 21% had a grade 3 TRAE.

Twenty-three percent of patients experienced any-grade AEs that led to treatment discontinuation, including 19% with a grade 3/4 AE and 2% with a grade 5 AE.

Immune-mediated AEs of any grade were observed in 46% of patients, including 16% with a grade 3/4 event. The rates of any-grade and grade 3/4 immune-mediated TRAEs were 33% and 16%, respectively.

“Adjuvant atezolizumab was well tolerated, and this single-arm study showed that outcomes were better than anticipated in patients who received adjuvant atezolizumab, which may prompt further studies of immuno-oncology monotherapy,” Carbone concluded.

Editor’s note: Dr Carbone reported serving as a consultant for Iovance Biotherapeutics and InThought; serving as an advisory board member for Janssen, Jazz, Sanofi Genzyme, Regeneron, GSK, Iovance Biotherapeutics, Arcus Biosciences, Roche, and Novartis; receiving honoraria from AstraZeneca; receiving speaking fees from Mirati, BMS Israel, Pfizer, and Roche Taiwan; serving on a data monitoring committee for Lilly; and participating in education programs for AstraZeneca and OncLive®.

References

1. Carbone DP, Waqar SN, Chaft JE, et al. Updated survival, efficacy and safety of adjuvant atezolizumab after neoadjuvant atezolizumab in the phase 2 LCMC3 study. Presented at: 2023 European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Abstract 145MO.
2. Chaft JE, Oezkan F, Kris MG, et al. Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial. Nat Med. 2022;28(10):2155-2161. doi:10.1038/s41591-022-01962-5