Efficacy And Safety Of Anti-PD-1 Monoclonal Antibody In The Treatment Of Advanced Malignant Tumors

Purposes:To investigate the efficacy and safety of the antibody to programmed cell death-1(PD-1)sintilimab(developmental number IBI08)in treatment of advanced malignant melanoma,lung cancer,neuroendocrine carcinoma,gastric cancer and other gastrointestinal cancer in China.Methods:From June 2017,according to the criteria for recruitment and exclusion,Chinese patients with advanced malignant melanoma,lung cancer,neuroendocrine carcinoma,gastric cancer and other gastrointestinal cancer including esophageal cancer,colorectal cancer,hepatocellular carcinoma,cholangiocarcinoma who are aged 18-70 years old,with an ECOG-PS of 0 or 1 and a life expectancy over 12 weeks were recruited.Patients received sintilimab at a dose of 200mg alone every three weeks or combined with standard chemotherapy every three weeks until disease progression,unacceptable toxicity,or other protocol-defined reasons for discontinuation.Safety,side-effect profile and efficacy were prospectively estimated by NCI CTCAE v4.03 and RECIST 1.1.,respectively.The primary endpoint was objective response rate,disease control rate,progression-free survival and overall survival.Results:Between June 2017 to December 2018,84 patients were screened and finally 63 patients consisting of 8 patients with malignant melanoma,23 patients with lung cancer,17 patients with gastric cancer,15 patients with other gastrointestinal cancer including esophageal cancer,colorectal cancer,hepatocellular carcinoma,cholangiocarcinoma and neuroendocrine carcinoma were enrolled.Among them,15 patients with advanced lung cancer and 17 with advanced gastric cancer received sintilimab combined with standard chemotherapy as first-line treatment,others who failed to standard chemotherapy or had poor tolerance to chemotherapy were given sintilimab monotherapy as salvage treatment.All of the 63 patients received 473 cycles of treatment and the media cycle was 7 cycles(1-23).Best efficacy of 53 patients was assessed.2 patients achieved an efficacy of CR and 21 patients had PR.Among these patients,ORR was 43.3%(23/53),DCR was 81.1%(43/53),the media PFS was 118 days(95%CI:96-140 days),the media OS was not reached due to the immature events.For all patients,there were 50 patients(79.3%)experienced treatment-related side-effect and among them 34 patients(54%)suffered side-effect associated with sintilimab.9 patients(14.3%)encountered grade 3-4 toxicities.The most common sintilimab-related toxicities were fatigue(14.3%),anemia(12.7%),leukopenia(9.5%)and neutropenia(7.9%).Sintilimab-related irAE occurred in 14.3%of the patients,including hypothyroidism(n=3,4.8%),interstitial pneumonia(n=3,4.8%),vitiligo(n=2,3.2%)and hyperthyroidism(n=1,1.6%).2 patients received sintilimab combined with standard chemotherapy discontinued the treatment,one with squamous cell NSCLC discontinued the treatment because of severe hematological toxicity,and another one with advanced gastric cancer discontinued the treatment because his impaired liver function didn’t recovery within 6 weeks’ treatment.And no patients died of sintilimab-related side-effect.Conclusions:Our data suggest that the efficacy of sintilimab in treating advanced malignant tumor was consistent with the findings about anti-PD-1 monoclonal antibodies reported by previous studies.And the safety profile was acceptable.It may lead to further randomized controlled studies to determine the role of sintilimab in treatment of malignant solid tumors.