Neoadjuvant Pembrolizumab and Chemotherapy in Resectable Clinical Stage III Non-Small-Cell Lung Cancer

A Retrospective Cohort Study

Guangyin Zhao; Hongyu Zhang; Fengkai Xu; Chunlai Lu; Qiaoliang Zhu; Francesco Grossi; Duilio Divisi; Teng Ma; Jie Gu; Di Ge


Transl Lung Cancer Res. 2023;12(1):141-149. 

In This Article

Abstract and Introduction


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.


Lung cancer is the principal causation for death globally, and nearly 85% of lung cancers are non-small-cell lung cancer (NSCLC).[1] A significant proportion of patients with NSCLC have locally advanced clinical stage III disease (c-III) at the time of diagnosis.[2] Outcomes for this subset of patients remained generally poor over the past few decades.[3] Neoadjuvant chemotherapy followed by surgical resection with or without adjuvant chemotherapy and thoracic radiotherapy in selected cases has become the standard treatment for patients resectable with this stage of NSCLC. Chemotherapy or chemoradiotherapy remains the conventional option for preoperative induction therapy. However, only a modest (approximately 5%) increase in 5-year overall survival (OS) has been achieved after perioperative (neoadjuvant or adjuvant) chemotherapy. Moreover, the combination of radiotherapy did not improve the prognosis, but increased the chance of complications.[4,5]

Nowadays, immune checkpoint inhibitors (ICIs), such as programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (ligand PD-L1) inhibitors, have been approved as first-line treatment for metastatic NSCLC patients, either as monotherapy or combined with chemotherapy. Recently, immunotherapy has been assessed for the early-stage curative treatment of NSCLC. As a neoadjuvant treatment, ICIs could stimulate the priming and expansion of neoantigen-specific T cells in the tumor before surgical resection, bringing benefits in long-term tumor control.[6,7] Forde and colleagues showed that two cycles of neoadjuvant nivolumab were well tolerated and resulted in a major pathological response (MPR) rate of 45.0% and a complete pathological response (CPR) rate of 10.0%.[8] Furthermore, the use of ICIs combined with chemotherapy followed by surgery appear to achieve higher MPR rates in patients with stage IB–IIIA NSCLC,[9] probably because of the synergistically boosted effects of chemotherapy in response to ICIs. Pembrolizumab, a humanized IgG4 antibody targeting PD-1, either used alone or in combination with chemotherapy has displayed flexible reliability and anti-tumor action in patients with advanced NSCLC.[10] However, pembrolizumab's capacity as a neoadjuvant drug in NSCLC has not been well analyzed. The objective of the study was to evaluate the safety and feasibility of neoadjuvant pembrolizumab plus chemotherapy in patients with potentially operable c-stage-III NSCLC, examining the pathological response and tolerability of this treatment. We present the following article in accordance with the STROBE reporting checklist (available at