The Lancet sub-issue: a new breakthrough in combined immunotherapy for stomach cancer! Paboli-Zhumonodini-lunvastini's immune combined anti-vascular program, the objective mitigation rate of first- and second-line treatment was 69%. Clinical discovery.

In 2020, the immunotherapy seems to have come up with a kind of attack that is elite, gnawing is the momentum of hard bones, and began to attack hard bone hair such as liver cancer and gastric cancer.if the treatment of cancer is less difficult, we have to work hard to give hope to more patients who hope for new therapies such as stars and moon.of course, immunotherapy pays more attention to methods.in the case of gastric cancer, PD-1 / L1 inhibitors are now turning their direction, instead of single drug attack, they choose to use combination therapy.as introduced by the odd cakes not long ago, the combination of pabolizumab + trastuzumab + chemotherapy has made a great breakthrough in HER2 gastric / esophageal adenocarcinoma.and this time, pabolizumab has to be praised again.recently, the data of phase II epoc1706 trial were published in the Lancet Oncology. The results of this Japanese trial showed that the objective remission rate in the first and second line treatment of gastric cancer reached an astonishing 69% [1]! In the treatment of gastric cancer, pabolizumab has failed: in the second-line treatment of phase III keynote-061 trial, it did not show advantages over paclitaxel chemotherapy; in the first-line treatment of keynote-062 test, pabolizumab combined with chemotherapy was not as good as monotherapy, and the benefit of single drug was limited to patients with PD-L1 CPS ≥ 10 [2-3].although pabolizumab can also treat gastric cancer patients with mismatch repair defect (dmmr) or high tumor mutation load (tmb-h), these patients do not account for the majority. For example, the proportion of gastric cancer patients with dmmr is less than 10%.if more patients want to benefit from immunotherapy, they have to switch to new programs.if you want to choose a partner, the new antiangiogenic drug, rivatinib, is a good partner. Its partner with pabolizumab has been approved by FDA for the treatment of endometrial cancer with MSI-H / dmmr, and has obtained the qualification of breakthrough therapy in liver cancer, renal cancer and other cancers.and the combination of anti angiogenesis drugs and PD-1 / L1 inhibitors can wipe out the synergistic mechanism of sparks from different angles. Singularity cake has mentioned it more than once. After all, this is the most significant direction of combined immunotherapy.are you familiar with this picture? This phase II trial included 29 patients with recurrent or metastatic gastric cancer, of whom 14 were first-line treatment and 15 were second-line treatment.but in other conditions, the test requirements are very broad, there is no restriction of HER2 negative and PD-L1 expression level positive.the enrolled patients were given 20 mg of rivatinib daily and 200 mg of pabolizumab every three weeks.since it is a phase II trial to evaluate the anti-tumor effect, the objective response rate (ORR) is the main end point of the trial. Based on the data from previous gastric cancer trials, the research team set the orr target value of combination therapy at 30%.it has been proved that this obviously underestimates the strength of pabolizumab + rivatinib.of the top 10 patients enrolled in the first stage of the trial, 6 patients achieved objective remission, which encouraged the research team to continue to complete the enrollment of 19 patients in the second stage. preliminary data from the epoc1706 trial were published at this year's ASCO Gastrointestinal Cancer Symposium (ASCO GI): the overall objective remission rate of patients is 69%, and the disease control rate is as high as 100%! The median progression free survival (PFS) of 29 patients was 7.1 months at the time of data analysis. even in the 9 patients with stable condition, 8 of them had tumor shrinkage, but they did not reach the partial remission criteria. It is worth noting that only two of these 29 patients belong to dmmr patients who are theoretically more suitable for immunotherapy. even if these two patients were excluded, the efficacy of the combination of pabolizumab and rivatinib was not bad in other patients, PFS and orr were 7.0 months and 70% respectively. at present, the overall median survival (OS) of the patients has not yet reached, but the survival rate of more than 70% at 12 months of treatment has also been better than the previous clinical trial data. after all, the feature of remission = long-term benefit is the biggest difference between immunotherapy and chemotherapy. to see how many patients who are still under treatment can maintain the benefit. In addition, the effect of biochemical markers such as PD-L1 expression level and tumor mutation load (TMB) were also analyzed. The Orr and PFS were significantly higher in patients with positive PD-L1 expression (CPS ≥ 1), especially in patients with CPS ≥ 10, but TMB level was not significantly associated with PFS. in terms of safety, the incidence of adverse events related to treatment above grade 3 was 48%, and the most common was hypertension (11 cases, 38%). However, it can be basically solved through dose adjustment and symptomatic medication, which shows that the safety of combined treatment is also guaranteed. in conclusion, the potential of combination therapy of pabolizumab and rivatinib in the treatment of gastric cancer is indeed very good. although the research team said in the paper that the effect of immunotherapy on patients in East Asia such as Japan is better than that in Europe and the United States, China, Japan and South Korea are high incidence areas of gastric cancer in the world. Wouldn't it be nice if the curative effect was better? 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