Best CP! There is a new breakthrough in the treatment of advanced gastric cancer in the combination of "k drug and lunvalitini".

Gastric cancer is the second largest cancer in China, accounting for nearly 50% of the world's morbidity and mortality. 80% of gastric cancer patients are in advanced stage at the time of diagnosis, and the treatment methods are very limited. The 5-year survival rate is only about 15%.at present, chemotherapy is still the first-line treatment for advanced gastric cancer, but the curative effect is limited, so we need to explore a more efficient treatment scheme.in recent years, the exploration of targeting and immunotherapy is in full swing.targeted and first-line immunotherapy for advanced gastric cancer have also been carried out.but unfortunately, none of them achieved satisfactory results.therefore, experts and scholars began to consider whether the combination of drugs can achieve the "1 + 1 & gt; 2" effect? "Cola combination" is the idea of using PD-1 monoclonal antibody combined with anti angiogenesis drugs, that is, the combination of "pabolizumab + rivatinib", which has been recognized as a breakthrough therapy by FDA in the fields of renal cell carcinoma, endometrial cancer and liver cancer.in the field of advanced gastric cancer treatment, "cola combination" is still brilliant.recently, the Lancet Oncology published a phase II clinical study on the efficacy and safety of the combination in patients with advanced gastric cancer and esophageal gastric junction adenocarcinoma (epoc1706). Results: the disease control rate was 100%, and the objective remission rate was as high as 69%! This combination shows excellent anti-tumor activity and brings new therapeutic hope to the patients who are looking forward to it.the star member of "cola group" 01, lenvatinib is a multi kinase inhibitor, which can inhibit VEGF receptor tyrosine kinase and other tyrosine kinases.pabolizumab (drug K) is a well-known anti-PD-1 antibody.studies have shown that rivarotinib has synergistic effect with K drug, which can not only block the immune escape pathway of PD-1, but also inhibit the immune escape "accomplice" - Tam when monocytes differentiate into tumor cells; at the same time, lovastatinib competitively inhibits the binding of VEGF and corresponding receptors, and inhibits the growth and differentiation of tumor cells and TAM; in addition, lovastatinib can inhibit the growth and differentiation of tumor cells and Tam by inhibiting the binding of VEGF and corresponding receptors Low level of tumor associated macrophages and increased infiltration of CD8 + T cells enhanced the antitumor activity of PD-1 inhibitors.Fig.1 the synergistic mechanism of K drug and rivarotinib.02 amazing data of "cola combination" in the treatment of gastric cancer. The epoc1706 study is an open label, one arm phase II trial to evaluate the efficacy and safety of "drug K + rivatinib" in patients with advanced gastric cancer and esophageal gastric junction adenocarcinoma.a total of 29 patients with recurrent or metastatic gastric cancer (27 PMMR, 2 dmmr; 14 first-line treatment and 15 second-line treatment) were enrolled in the study, without HER2 negative and PD-L1 positive expression levels. The median follow-up time was 12.6 months.the patients were orally given 20 mg of rivarotinib a day and 200 mg of pabolizumab every 3 weeks until the disease progressed or intolerable toxicity.in order to evaluate the antitumor effect, the objective response rate (ORR) was used as the primary endpoint.the specific research results are as follows: 1. The objective response rate (ORR) was as high as 69%, and 20 (69%) of 29 patients achieved objective remission.excluding two patients with dmmr, the orr of the remaining 27 patients still reached 70%. and the orr of patients receiving first-line and second-line treatment was similar. Figure 2 the efficacy of "K drug + rivarotinib" treatment was waterfall chart 2 disease control rate (DCR) was as high as 100%. Of 29 patients, 1 (3%) achieved complete remission, 19 (66%) achieved partial remission, and the remaining 9 (31%) patients were stable, and the tumor size of 8 of these 9 patients decreased. that is, all patients' conditions have been controlled, and the disease control rate is as high as 100%. Table 1: efficacy data of "K drug + rivarotinib" treatment. 3. The median progression free survival time was 7.1 months. The median overall survival time was not reached, but the 12-month survival rate was more than 70%. this lifetime survival rate has also been higher than the current clinical trial data, which shows the characteristics of long-term survival of immunotherapy. Figure 3: OS and PFS follow-up data of "K drug + rivarotinib" treatment. Exploratory analysis of 4 studies showed that the orr of patients with PD-L1 positive score CPS ≥ 10, CPS ≥ 1 and CPS < 1 was 100%, 84% and 40%, respectively. the tumor burden (TMB) of 21 patients could be evaluated, and the orr of patients with high TMB (TMB & gt; 10) was higher than that of patients with low TMB (82% and 60%, respectively). it is worth noting that in the phase III clinical study (keynote-062) of first-line treatment of PD-L1 positive advanced gastric cancer with single drug K, Orr was only 16%, and PFS was only 2.0 months. no patients achieved objective remission in the phase 1 clinical trial of single drug ramvastinib. however, the combination of these two drugs has greatly improved the clinical efficacy and achieved amazing results. this fully demonstrates the advantages of combination therapy compared with previous clinical results of monotherapy. safety analysis: the incidence of adverse events related to the combined treatment of grade 3 and above was 48%. The most common adverse events were hypertension (11 cases, 38%), proteinuria (5 cases, 17%), and most of them were reversible. no grade 4 treatment-related adverse events occurred. the adverse reactions can be solved through dose adjustment and symptomatic medication, which shows that the safety of combined treatment is guaranteed. "K drug + rivatinib" showed excellent antitumor activity and good safety in the treatment of patients with advanced gastric cancer. although more confirmatory clinical trials are needed due to the small number of samples, it is worth mentioning that the enrolled population is mainly the East Asian population in Japan, and China, Japan and South Korea are the high incidence areas of gastric cancer in the world, so the data is more worthy of looking forward to. "cola combination" has carried out a number of clinical studies in China, and the first-line clinical trials in endometrial cancer, NSCLC and liver cancer have entered phase III, and their efficacy has been tested through a large number of clinical studies. we hope that this "King fried combination" will bring dawn to the treatment of patients with advanced gastric cancer. references kawazoe a, Fukuoka s, Nakamura y, et al. Lentinib plus pembrolizumab in patients with advanced gastric cancer in the first line or second line setting (epoc1706): an open label, single arm, phase 2 trial [J]. The Lancet Oncology, 2020