Two cycles versus three cycles of neoadjuvant sintilimab plus platinum-doublet chemotherapy in patients with resectable non-small-cell lung cancer (neoSCORE): A randomized, single center, two-arm phase II trial.
Authors: Qiu Fuming , Fan Junqiang , Shao Miner , Yao Jie , Zhao Lufeng , Zhu Ling , Li Baizhou , Fu Yanbiao , Li Lili , Yang Yunben , Wang Yunke , Chen Mengyao , Xie Wanglan , Zhang Xinyi , Tu Jinglian , Chen Xiaoke , Wu Zuqun , Chen Zexin 
Published: June 2022

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Background: Neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy have a promising efficacy in resectable non-small-cell lung cancer (NSCLC), yet the period of neoadjuvant immunochemotherapy is undetermined. This phase II study compared the efficacy and safety of two cycles with three cycles of neoadjuvant sintilimab plus chemotherapy in resectable stage IB-IIIA NSCLC. Methods: This randomized, open-label phase II trial recruited patients aged 18 or older with histologically confirmed, treatment-naïve, American Joint Committee on Cancer-defined stage IB-IIIA, resectable NSCLC. Eligible patients were randomly assigned to two or three cycles of neoadjuvant treatment with intravenous sintilimab (200 mg) plus carboplatin (area under curve 5) and nab-paclitaxel (260mg/m2, for squamous) or pemetrexed (500mg/m2, for non-squamous) on day 1 of three-week cycle. After surgical resection, patients received totally four doses of perioperative immunochemotherapy, followed by one-year sintilimab maintenance under patient decision. Randomisation was stratified by tumor PD-L1 expression (≥1% vs < 1%). The primary endpoint was MPR rate. Secondary endpoints included complete pathology response (pCR) rate, objective response rate (ORR), 2-year disease-free survival (DFS) rate, 2-year overall survival (OS) rate and safety. This trial is registered with ClinicalTrials.gov, number: NCT04459611. Results: From 6/2020 to 9/2021, 60 patients were enrolled and received neoadjuvant treatment. The patient characteristics of both arms were well balanced. Among 55 patients with successful R0 resection, we observed a higher MPR rate (41.4%, 12/29) in three-cycle group compared with two-cycle group (26.9%, 7/26) (p = 0.260), meanwhile, pCR rate achieved 24.1% (7/29) and 19.2% (5/26) respectively (p = 0.660). Patients of squamous subtype generally achieved a statistically higher MPR rate (51.6%, 16/31) compared with the non-squamous subtype (12.5%, 3/24) (p = 0.002). In squamous subgroup, three cycles neoadjuvant treatment induced a MPR rate of 60% compared with 43.8% after two cycles treatment (p = 0.366).In the meantime, the MPR rate was 21.4% versus 0% in non-squamous subgroup, respectively (p = 0.239). The ORR showed no statistical difference between three-cycle group (55.2%, 16/29) and two-cycle (50%, 13/26) (p = 0.701). Patients were well-tolerated in both groups and 5% (3/60) experienced grade 3 immune related adverse events. Conclusions: It is the first randomized study comparing different treatment periods of immuno-chemotherapy in the neoadjuvant setting. Three cycles neoadjuvant treatment achieved a numerically higher MPR rate compared with two cycles. Patients with squamous lung cancer obtained a better MPR rate compared with non-squamous subtype. Clinical trial information: NCT04459611.