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

BackgroundAn 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.MethodsThis 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.ResultsAn 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).ConclusionsNeoadjuvant 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 Registrationhttps://clinicaltrials.gov/ct2/show/NCT04197076?recrs=a&cond=NCT04197076&draw=2&rank=1.

Neoadjuvant Chemoimmunotherapy for NSCLC

“…Overall, there was a low risk of bias among RCTs, with bias arising due to unbalanced treatment arms in 1 study and potentially multiple analyses of the same data in another study (eFigure 2 in Supplement 1). For nonrandomized studies, bias concerns were mostly associated with inadequate length of follow-up (eTable 4 in Supplement 1).…”

“…After title and abstract screening, 519 studies were excluded, and an additional 41 studies were removed after full-text screening. A total of 42 publications and 6 abstracts met inclusion criteria, including 43 trials and 5 follow-up studies, from which we extracted 54 study arms; 5431 patients were included overall in the 43 trials (4020 males [74.0%]; median age range, 55-70 years) (Table; eTable 3 and eFigure 1 in Supplement 1). There were 8 RCTs comparing neoadjuvant chemoimmunotherapy with chemotherapy, namely CheckMate 816, KEYNOTE-671, NADIM II, AEGEAN, Neotorch, Checkmate 77T, TD-FOREKNOW, and RATIONALE 315 (Table).…”

“…Across 3387 patients (2582 males [76.2%]; median age range, 61-66 years) included in 8 RCTs, there were 1688 patients (49.8%) treated with chemotherapy, 1699 patients (50.2%) treated with chemoimmunotherapy, 1882 patients (55.6%) who had squamous histology, and 2443 patients (72.1%) who had stage III disease. Across all studies, there were 27 neoadjuvant chemotherapy and 27 neoadjuvant chemoimmunotherapy arms; 21 arms included only patients with stage III disease. Studies ranged from 10 patients to 400 patients per arm, and there were 2347 patients assigned to neoadjuvant chemoimmunotherapy and 3084 patients assigned to neoadjuvant chemotherapy.…”

“…We also compared these clinical variables across all trials, including RCTs and nonrandomized single-arm trials . For single-arm studies, there was also a significantly higher MPR and pCR for chemoimmunotherapy than chemotherapy (eFigures 27-28 in Supplement 1).…”

Recent death early warning value of ECG changes in patients with NSCLC

“…Once diagnosed, the best time for surgery is often missed. [4] Chemotherapy and radiotherapy use chemicals or radiation to destroy the chromosomes of cancer cells and stop them from growing. [5][6][7][8][9] These treatments inevitably have cardiotoxicity and side effects.…”