The characteristics of long-lasting responders to PD-1 inhibitor in advanced non-small cell lung cancer patients

Abstract

Background: We often experience long-lasting response of PD-1 inhibitor in advanced NSCLC patients. However, the characteristics associated with long-lasting response to PD-1 inhibitor is still unknown. In this study, we investigated the characteristics of patients who showed long-lasting (≥2 years) response to anti-PD-1 antibodies. Methods: We reviewed consecutive advanced NSCLC patients who received a PD-1 inhibitor monotherapy (nivolumab, or pembrolizumab) between December 22, 2015 and May 31, 2017 at National Cancer Center Hospital in Japan. The cut-off date was June 1, 2019. We defined patients who obtained clinical benefit for more than 6 months as “Responders”. Among them, those who had a durable response for more than 2 years were defined as “Long-term responders” (LTR), and those who responded or shorter than 2 years as “Non-LTR”. We investigated the patient baseline characteristics and clinical outcomes of anti-PD-1 monotherapy including objective response rate (ORR) and maximal tumor shrinkage. Tumor response was assessed by RECIST version 1.1. The PD-L1 expression on tumor cells was assessed by using 22C3 antibody. Results: A total of 232 patients were included in this analysis. Responders accounted for 37.9 % (88 out of 232). Of these patients, 31 (35.2%) were LTR group and 57 (64.8 %) were non-LTR group. At the time of data cut off, 22 (71.0%) of 31 patients in LTR group showed lasting response of PD-1 inhibitor. There were no significant differences in the baseline characteristics such as age, sex, performance status, driver mutation, clinical stage, and smoking status. Regarding histological distribution, non-squamous cell histology was more common in the LTR group (68% vs. 90%, P = 0.021). The ORR in the LTR group was significantly higher than non-LTR group (80.6% vs. 32.0%, P <0.0001). The median tumor shrinkage (range) in the LTR group was also significantly higher than that in the non-LTR group [72.8 (range: 6.8-100)% vs 48.7(range: 3.9-100)% (P=0.0002)]. In contrast, no difference was found in the PD-L1 expression between two groups (P = 0.213). Conclusion: Long-lasting response of PD-1 inhibitor was particularly characterized by high tumor shrinkage in patients who had response to PD-1 inhibitors. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: Y. Okuma: Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Chugai. Y. Goto: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony, Research grant / Funding (institution): ONO; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Shionogi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Glaxo Smith Kline; Advisory / Consultancy: Guardant Hearlth; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Dai-ichi Sankyo; Research grant / Funding (institution): Kyorin. H. Horinouchi: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZaneca; Adv sory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): ONO; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol Myers Squibb; Speaker Bureau / Expert testimony: Kyowa-kirin; Research grant / Funding (institution): Abbvie; Speaker Bureau / Expert testimony: Dai-ichi Sankyo; Research grant / Funding (institution): Kyorin; Research grant / Funding (institution): Genomic Health. N. Yamamoto: Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy: Otsuka; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy: Cimic; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (institution): ONO; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Kyowa-Hakko Kirin; Research grant / Funding (institution): JansenPharma; Research grant / Funding (institution): MSD. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): ONO; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristrol-Myers Squibb; Honoraria (self): Boehringer lngelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): Taiho; Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Advisory / Consultancy: Celltrion; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Dainippon Sumitomo; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Kissei; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Daiichi-Sankyo. All other authors have declared no conflicts of interest.