Neoadjuvant pembrolizumab and chemotherapy in resectable clinical stage III non-small-cell lung cancer: a retrospective cohort study

Abstract

Background: Pembrolizumab has been shown to be effective and safe in improving the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, the effectiveness and safty of pembrolizumab in the induction treatment of patients with potential resectable clinical stage III NSCLC remains undetermined.

Methods: A total of 25 patients who received neoadjuvant pembrolizumab plus chemotherapy for preoperative stage III NSCLC between August 2020 and November 2021 in Zhongshan Hospital were retrospectively evaluated, and 21 of them were followed by pulmonary resection. The neoadjuvant treatment was as follows: intravenous pembrolizumab (200 mg) on day 1, carboplatin [target area under the curve (AUC) 5 mg/mL] or cisplatin (75 mg/m²) on day 1, and pemetrexed (500 mg/m² for adenocarcinoma) or nab-paclitaxel (260 mg/m² for other subtypes) on day 1 of every 21-day cycle up to two or three cycles.

Results: The mean age of all 25 patients was 65 years, of whom 22 were men and 3 were women. Seventeen were diagnosed before treatment as clinical stage IIIA, seven as IIIB, and one as IIB. All received neoadjuvant immunotherapy plus chemotherapy. Following induction therapy, 21 patients with stable disease or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) underwent surgical resection without delay. Among the patients who underwent operation, major pathological response (MPR) was achieved in 13 patients, including 6 (28.6%) patients achieved a complete pathological response (CPR). Two patients with partial radiologic remission refused operative treatment, one had progressive disease (PD), and another developed a grade immune pneumonia and could not tolerate surgery. However, none of the adverse events caused surgery delays or deaths.

Conclusions: Neoadjuvant pembrolizumab plus chemotherapy could be considered reliable for clinical stage III NSCLC, but needs to be validated with more robust clinical trials.

Keywords: Non-small-cell lung cancer (NSCLC); complete pathological response (CPR); major pathological response (MPR); neoadjuvant therapy; treatment-related adverse event (trAE).

Figure 1

Disease evolution under neoadjuvant pembrolizumab and chemotherapy. The CT scan shows significant regression of the primary tumor and metastatic mediastinal lymph nodes after neoadjuvant immunochemotherapy. The red arrows indicate tumor and mediastinal lymph node.