Melanoma immunotherapy! The combination of bestimer opdivo + yervoy in phase III clinical failed to improve the recurrence free survival of patients with PD-L1 < 1%!

November 21, 2019 / BIOON / -- Bristol Myers Squibb (BMS) recently announced one of the common primary endpoints of checkmate-915 in the phase III clinical study of melanoma immunotherapy Checkmate-915 is a randomized, double-blind, placebo-controlled study conducted in patients with stage IIIB / C / D or stage IV (no signs of disease) melanoma to evaluate the efficacy of opdivo (odivo, common name: nivolumab, nevumab) and yevoy (ipilimumab, eplimuma) immunocombination therapy (oy combination) relative to opdivo single drug treatment In addition to surgery for melanoma lesions and / or adjuvant radiotherapy after neurosurgery for central nervous system lesions, the patients in the study have not received cancer treatment for melanoma before In this study, a total of 1934 patients were randomly assigned to receive oy combination therapy (opdivo 240mg, once every two weeks intravenous infusion; yevoy 1mg / kg, once every six weeks intravenous infusion) or opdivo single drug treatment (480mg, once every four weeks intravenous infusion) for one year The published results show that in high-risk melanoma patients with tumor resection and expression of PD-L1 < 1%, the common primary end point of recurrence free survival (RFs) of oy combination did not reach a statistically significant improvement compared with that of opdivo alone The DMC recommended that the study remain unchanged The study remains double-blind and will continue to assess the RFs common primary endpoint in all patients (intention to treat, ITT) Melanoma is a kind of skin cancer, which is characterized by uncontrolled growth of melanocyte in the skin Metastatic melanoma is the most lethal form of the disease, when cancer cells have spread from the surface of the skin to other organs of the body The incidence rate of melanoma has been increasing steadily in the past 30 years In the United States, an estimated 912700 new melanoma cases were confirmed in 2018, with more than 9320 deaths The WHO estimates that by 2035, the incidence rate of melanoma will reach 424102 people, and the number of deaths will reach 94308 Melanoma can be divided into 5 stages (0-4 stages) according to its in situ characteristics, thickness and degree of ulceration, whether the tumor spreads to the lymph node or not, and the extent of tumor spreading beyond the lymph node Stage 3 melanoma usually has reached the local lymph nodes, but has not spread to distant lymph nodes or other parts of the body (metastasis), so it is necessary to resect the primary tumor and related lymph nodes Some patients can also receive postoperative adjuvant treatment Despite surgical resection, most patients experience relapse and metastasis In the early stage, melanoma is mostly curable, but if it spreads to local lymph nodes (stage 3), the survival rate will be reduced by about half In the United States, patients diagnosed with advanced melanoma (stage 4) have a 5-year survival rate of 15% - 20%, and a 10-year survival rate of 10% - 15% Clinically, the effective treatment of tumor has always been surgical resection, in addition to surgical treatment are called adjuvant treatment The purpose of adjuvant therapy is to eliminate the residual micrometastasis, reduce the chance of tumor recurrence and metastasis, and improve the cure rate Early intervention with adjuvant therapy has been shown to be an important factor in reducing the risk of postoperative recurrence in patients with high-risk stage 3 melanoma Approved in July 2014, opdivo is the first PD-1 immunotherapy on the market in the world In terms of melanoma, opdivo has approved three indications: (1) as a single drug therapy for patients with non resectable or metastatic melanoma; (2) in combination with yervoy for patients with non resectable or metastatic melanoma; (3) as an adjuvant therapy for patients with lymph node involvement or metastatic melanoma who have been completely removed Opdivo and yevoy are tumor immunology (I-O) therapies They target different regulatory elements in the immune system and use the immune system of human body to fight against tumors Opdivo targets to block PD-1 / PD-L1 pathway, yevoy targets to block CTLA-4 In October 2015, opdivo and yevoy combination therapy (oy) was approved as the first I-O combination therapy for metastatic melanoma At present, the indication has been approved by more than 50 countries in the world Up to now, the indications approved by oy combination are: (1) treatment of unresectable or metastatic melanoma; (2) first-line treatment of advanced renal cell carcinoma (RCC) patients; (3) treatment of high microsatellite instability (MSI-H) or mismatch repair defect (dmmr) metastatic colorectal cancer (CRC) in children and adults aged 12 and over At the end of September this year, BMS announced the five-year results of phase III clinical research of melanoma at the annual meeting of European Society of Oncology (ESMO) in 2019 This study was carried out in patients with advanced metastatic melanoma who had not been treated before (primary treatment), and evaluated the efficacy and safety of oy combination, opdivo single drug therapy and yevoy single drug therapy in the first-line treatment The 5-year results presented at this meeting represent the longest follow-up time to evaluate a dual immunooncology (I-O) therapy in a randomized controlled phase III study, and the long-term efficacy seen in the 5-year data demonstrates the importance of dual immunooncology therapy Data continue to show that the oy combination improves overall survival (OS) in patients with advanced metastatic melanoma compared to yevoy monotherapy At least 60 months (5 years) of follow-up, the 5-year overall survival rates of oy group, opdivo group and yevoy group were 52%, 44% and 26%, respectively Of the patients in the oy group who were still alive at 5-year follow-up, 72% remained untreated In patients with BRAF mutant and wild-type tumors, the 5-year overall survival rates were 60% and 48% for oy combination treatment, 46% and 43% for opdivo single drug treatment, and 30% and 25% for yevoy single drug treatment, respectively Health related quality of life continued to be maintained during opdivo monotherapy or oy combination therapy Original source: Bristol Myers Squibb announcements update on checkmate - 915 for opdivo (nivolumab) plus yevoy (ipilimumab) versus opdivo alone in patients with reset high risk melanoma and PD-L1 < 1%