An open, observational, three-arm clinical study of 2-3 cycles of treatment as neoadjuvant therapy in operable locally advanced non-small cell lung cancer: An interim analysis

Abstract

Background: An open, observational, three-arm clinical study aimed at investigating the efficacy of different neoadjuvant therapies (neoadjuvant immunotherapy with(out) chemotherapy, neoadjuvant chemotherapy, and neoadjuvant targeted therapy) in operable locally advanced non-small cell lung cancer (NSCLC) was conducted (NCT04197076). We report an interim analysis of 49 of 53 evaluable patients.

Methods: This study was conducted at Shanghai Chest Hospital and included eligible NSCLC patients who were 18 years old and had clinical stage IIB-IIIB disease. All 49 patients had surgical resection within 4-6 weeks after 2-3 cycles of neoadjuvant treatment consisting of immunotherapy (24 patients), chemotherapy (16 patients), and a targeted therapy (9 patients) regimen starting on the first day of each 21-day cycle. Pathologic complete response (pCR) was evaluated as the primary endpoint. Major pathological response (MPR) and tumor regression rate (TRR) were also evaluated.

Results: An improved pathologic complete response was achieved in the neoadjuvant immunotherapy arm compared with the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy arm [20.8% (5/24) vs. 6.3% (1/16) vs. 0.0% (0/9); P = 0.089, 95% CI 0.138-0.151]. More importantly, we found that the curative effect of the neoadjuvant immunotherapy arm in pCR+MPR was better than that of the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy arm [45.8% (11/24) vs. 18.8% (3/16) vs. 0.0% (0/9); P = 0.006, 95% confidence interval, 0.008-0.012]. Different neoadjuvant therapies had a statistically significant effect on postoperative pathological tumor downstaging (P = 0.017).

Conclusions: Neoadjuvant immunotherapy was associated with a trend toward better pCR than the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy. Curative effect (pCR + MPR) was significantly better with neoadjuvant immunotherapy (P = 0.006, 95% confidence interval, 0.008-0.012).

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT04197076?recrs=a&cond=NCT04197076&draw=2&rank=1.

Keywords: clinical trial; major pathological response; neoadjuvant therapy; operable locally advanced NSCLC; tumor regression rate.

Conflict of interest statement

Author JW is employed by GenomiCare Biotechnology (Shanghai) Co, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Gu, Wang, Sun, Xu, Niu, Zhao, Yao, Jian, Han, Wei, Chen and Lu.

Figures

Figure 1

Waterfall plots. (A) The tumor regression and number of each type of all patients who underwent neoadjuvant therapy (N = 53). (B) The tumor regression of the patients who underwent neoadjuvant immunotherapy and their PD-L1 expression (N = 25).

Figure 2

Boxplot of the tumor regression rate after two cycles of different treatments as neoadjuvant therapy in operatable locally advanced NSCLC. (N = 53).

Figure 3

Swimming plot of progression-free survival in the patients who underwent surgery. (N = 49). Each bar represents one patient. The left column shows clinical characterestics. Date cutoff was Nov. 4, 2021, sixteen (32.7%) patients who underwent surgery had disease progression, five (10.2%) of whom died. Of the 14 patients with pCR or MPR, one patient who received neoadjuvant immunotheraphy had disease progression. Of the 16 (one patient has died), 5 patient received neoadjuvant immunotheraphy (four patients have died), and 3 patients received neojuvant targeted chemotheraphy.