Immunotherapy for esophageal cancer! Bosimer opdivo (odevo) received the first regulatory approval, regardless of PD-L1, which significantly extended the life span!

February 22, 2020 / BIOON / -- Bristol Myers Squibb (BMS) recently announced that MHLW (Ministry of health, labor and welfare) of Japan has approved the anti PD-1 therapy opdivo (odivo, common name: nivolumab, nevuliumab), which is used for the unresectable advanced or recurrent esophageal cancer patients who are in progress after chemotherapy It is worth mentioning that this approval is the first approval of opdivo in the treatment of advanced esophageal cancer, and it is also the first immunooncology treatment plan approved in Japan In clinical studies, regardless of the expression of PD-L1, compared with chemotherapy, opdivo significantly prolonged the survival period and improved the overall quality of life The drug will provide an important second-line treatment for patients with advanced esophageal cancer This approval is based on the results of phase III clinical trial (ono-4538-24 / ca209-473; nct02569242) This is a multicenter, randomized, open label, global study to evaluate the efficacy and safety of opdivo versus chemotherapy (docetaxel or paclitaxel) in patients with unresectable advanced or recurrent squamous cell carcinoma (ESCC) who are refractory or intolerant to combination therapy of first-line fluorouracil and platinum drugs Patients were enrolled mainly in Asia, and up to 96% of the patients in the two treatment groups came from Asia In the study, patients were treated until the disease worsened or the toxicity was unacceptable The primary end points of the study were overall survival (OS), and secondary end points included investigator assessed overall remission rate (ORR), progression free survival (PFS), disease control rate (DCR), duration of remission (DOR), and safety The study was sponsored by Ono Pharma, an opdivo partner of Bristol Myers Squibb The results of the study were presented at the annual meeting of the European Society of Oncology (ESMO) in late September 2019, and simultaneously published in the Lancet Oncology Data showed that the study reached the primary end point of OS: compared with the chemotherapy group, the opdivo group showed a statistically significant improvement in OS, a 23% reduction in risk of death (HR = 0.77, 95% CI: 0.62-0.96, P = 0.019), a 2.5-month extension of median OS (10.9 months [95% CI: 9.2-13.3] vs 8.4 months [95% CI: 7.2-9.9]) The 12-month survival rate (OS) in the treatment group and chemotherapy group was 47% (95% CI: 40-54), 34% (95% CI: 28-41), and the 18-month survival rate (OS) was 31% (95% CI: 24-37), 21% (95% CI: 15-27), respectively Regardless of the level of PD-L1 expression, the survival benefit of opdivo was observed An exploratory analysis of the results reported by the patients showed that compared with chemotherapy, the quality of life of the patients treated with opdivo had a significant overall improvement For orr, 19% (95% CI: 14-26) and 22% (95% CI: 15-29) were in the opdivo group and the chemotherapy group, respectively However, studies have shown that opdivo significantly prolonged the median duration of remission (DOR: 6.9 months [95% CI: 5.4-11.1] vs 3.9 months [95% CI: 2.8-4.2]) compared to chemotherapy At the end of the data period, 7 patients in the opdivo treatment group remained in remission, and 2 patients in the chemotherapy group In terms of PFS, there was no significant difference between the treatment group and the chemotherapy group (HR = 1.08 [95% CI: 0.87-1.34]) In this study, the safety of opdivo was consistent with previous studies in ESCC and other solid tumors Compared with chemotherapy, the incidence of treatment-related adverse events (RAE) in opdivo patients was 60% and 95% respectively The incidence of three or four levels of trea was lower in the opdivo group than in the chemotherapy group (18% vs 63%), and the proportion of patients who experienced trea leading to drug withdrawal was the same in both groups (9%) Fouad namouni, head of oncology development at Bristol Myers Squibb, said: "together with our partner Ono Pharma, we are proud to offer opdivo as an alternative to chemotherapy for Japanese esophageal cancer patients, regardless of their PD-L1 status This is the first time that Opdivo has been approved in esophageal cancer, reflecting our commitment to advancing treatment options to extend the survival of patients with refractory gastrointestinal cancer " Esophageal cancer is the seventh most common cancer in the world and the sixth leading cause of cancer death The five-year relative survival rate for patients diagnosed with metastatic disease was 8% or less The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, accounting for 90% and 10% of all esophageal cancer cases, respectively It is estimated that 572000 new cases are confirmed each year, and about 500000 people die of esophageal cancer Most of the cases were diagnosed as advanced diseases, which affected the patients' daily life, including eating ability Asia has the highest incidence of esophageal cancer, with 444000 confirmed cases every year, accounting for 80% of the world's cases of esophageal cancer Every year, 20000 cases are diagnosed and 12000 people die of esophageal cancer in Japan In the aspect of immunotherapy for esophageal cancer, at the end of July 2019, keysruda (coreda, common name: pembrolizumab, pabolizumab) was approved by FDA of the United States to treat patients with ESCC with PD-L1 positive Specifically, it was approved by an FDA Approved test methods identified patients with recurrent, locally advanced, or metastatic ESCC who expressed PD-L1 (with a positive score of [CPS] ≥ 10) and progressed after one or more systemic therapies Keytruda is the first anti-PD-1 therapy approved for patients with recurrent locally advanced or metastatic ESCC (tumor expression of PD-L1, CPS ≥ 10) The approval was based on data from two clinical studies keynote-181 (nct02564263) and keynote-180 (nct02559687) Data from the keynote-181 study showed that in ESCC patients with tumor expression of PD-L1 (CPS ≥ 10), keytruda treatment improved OS compared with chemotherapy (median OS: 10.3 months [95% CI: 7.0-13.5] vs 6.7 months [95% CI: 4.8-8.6]; HR = 0.64 [95% CI: 0.46-0.90]) Data from the keynote-180 study showed that in 35 ESCC patients with tumor expression of PD-L1 (CPS ≥ 10), Orr was 20% (95% CI: 8.0, 37.0) In 7 patients with remission, DOR ranged from 4.2 months to 25.1 + months, 71% patients (5 cases) dor ≥ 6 months, 57% patients (3 cases) dor ≥ 12 months Original source: 1 Japan industry of health, Labor and Welfare Approves Opdivo (nivolumab) for the Treatment of Patients with Unresectable Advanced or Recurrent Esophageal Cancer 2、 Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial