New advances in drugs. Best CP! Paboli Zuma Anti-Combination Rwantinib Treatment of Advanced Gastric Cancer ORR Up to 69%

Gastric cancer is one of the most common malignant tumors of digestive system. It has strong heterogeneity, few effective treatments and poor prognosis.the efficacy of immunotherapy alone is still limited in gastric cancer, and the strategy of combined immunotherapy has gradually become the direction of exploration. Many attempts have been made in the field of gastric cancer, such as immunotherapy combined with chemotherapy and anti angiogenesis therapy.rivatinib is a multi kinase inhibitor that can inhibit VEGF receptor tyrosine kinase and other tyrosine kinase types.in animal experiments, it can significantly reduce the level of tumor associated macrophages and increase the infiltration of CD8 positive T cells, thus enhancing the antitumor activity of PD-1 inhibitors.the results of mid-term analysis of the combination therapy for advanced endometrial cancer showed that the orr of combination regimen was 38.0% at 24 weeks, and the orr of MSI-H / dmmr subgroup was 63.6%.based on the results, rivarotinib combined with pabolizumab has been approved by FDA for non MSI-H / dmmr patients with advanced endometrial cancer who have progressed after systemic treatment but are not suitable for radical surgery or radiotherapy.recently, the Lancet Oncology published the data of phase II epoc1706 trial. The results showed that the objective remission rate of pabolizumab combined with rivatinib in the first and second line treatment of gastric cancer reached an amazing 69%! The study was an open single arm phase II trial at the East Hospital of the National Cancer Research Center of Japan.patients aged 20 years or older with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma with ECoG of 0 or 1 and measurable lesions according to recist1.1, regardless of treatment.study methods the enrolled patients received 20 mg oral lovastatin and 200 mg pabolizumab intravenously every 3 weeks until disease progression or intolerable toxicity or withdrawal of consent.the primary endpoint was the objective response rate (ORR), and all eligible patients who had received at least one protocol treatment were analyzed.safety analysis includes all patients who have received at least one protocol treatment, whether they are qualified or not.results from October 15, 2018 to March 25, 2019, 29 patients with recurrent or metastatic gastric cancer (27 with MSS and 2 with MSI; 14 with first-line treatment and 15 with second-line treatment) were enrolled in the study.the median follow-up time was 12.6 months (IQR 10.5-14.3), and 20 of the 29 patients (69%, 95% CI 49-85) achieved remission.excluding two patients with mismatch repair defects, the orr of the remaining 27 patients still reached 70%.patients receiving first-line and second-line treatment had similar orr, with a disease control rate (DCR) of 100%. The median progression free survival was 7.1 months (95% CI 5.4-13.7), and the median overall survival was not yet achieved.exploratory analysis showed that orr was 84% in PD-L1 positive patients and 40% (4 / 10) in PD-L1 CPS & lt; 1 patients.tumor mutation load (TMB) was assessed in 21 patients, with an orr of 82% in patients with high TMB (TMB & gt; 10) and 60% in patients with low TMB. the most common level 3 adverse events associated with treatment were hypertension (11 cases [38%]), proteinuria (5 cases [17%]) and thrombocytopenia (2 cases [7%]), most of which were reversible. there were no grade 4 treatment-related adverse events and serious treatment-related adverse events or death events. conclusion pabolizumab + rivatinib has promising antitumor activity and acceptable safety in patients with advanced gastric cancer. in the phase III trial keynote-062, the orr of patients with advanced gastric cancer whose pd-l1cps ≥ 1 was treated with pabolizumab as the first-line treatment was 16%, and PFS was only 2.0 months. in the phase 1 clinical trial, no patient achieved objective remission. however, in the epoc1706 study, Orr reached 69%, PFS reached 7.1 months, and no patients developed disease at the first assessment. these results suggest that the combination therapy is more effective than the previous clinical results of monotherapy. this is also consistent with the high antitumor activity reported in other solid tumors. the latest data on the treatment of unresectable hepatocellular carcinoma (HCC) with pabolizumab combined with rivatinib was reported at the ASCO meeting in 2020. A total of 104 patients were enrolled and 100 patients were included in the first-line analysis. According to the mrecist standard, Orr was as high as 46%, the median OS was extended to 22 months, and PFS was 9.3 months. in addition, pabolizumab combined with rivatinib is being carried out in renal cell carcinoma, non-small cell lung cancer, melanoma and other tumor species, and the future is expected. References: 1. Kawazoe a, Fukuoka s, Nakamura y, et al. Lenvatinib plus pembrolizumab in patients with advanced gas cancer in the first line or second line setting (epoc1706): an open label, single arm, phase 2 trial [J]. The lancet ontology, 2020.2.zhu a x, Finn r s, Ikeda m, et al. A Phase 1b Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma (uHCC). 2020 ASCO, abs 4519.