Today's "King Blast" combination is the star of the joint therapy.

Can patients with advanced cancer usher in a new era of targeted immunotherapy? DCR 100%？！ In the field of gastric cancer, the "King fried" combination shows the strength of the king! Recently, a study on the efficacy and safety of "rivatinib + pabolizumab" in advanced gastric cancer and esophagogastric junction cancer was published in Lancet Oncology.the results showed that according to RECIST v1.1 criteria, the orr (objective response rate) of all patients was 69%, including Cr (complete remission) rate was 3%, PR (partial response) rate was 66%, and orr of PMMR (normal mismatch repair) was 70%.the MPFs (median progression free survival) of gastric cancer patients treated with "Wang Zhi" combination therapy was 7.1 months (95% CI: 5.4-13.7) [1], which means that patients with advanced gastric cancer will usher in a new combination therapy! Not only is gastric cancer, "Wang fried" combination in the field of liver cancer also show their skills! Through a number of clinical trial data of liver cancer, the efficacy of combined use of rivarotinib and pabolizumab is better.at the same time, the combination of "Wang Chao" also showed good performance in the treatment of eight kinds of cancer (Table 1).Table 1: summary of the efficacy of rivatinib in multiple types of cancer. Under the background that China is a big country with liver cancer, there is a long way to go to improve the survival period of patients with liver cancer.in recent years, targeted therapy and immunotherapy for liver cancer have sprung up rapidly. As an important therapeutic drug, lovastatin has brought real hope for liver cancer patients in China.in the field of liver cancer treatment, there are both keynote-524 trial and leap-002 phase III clinical trial.at the recent 2020 ASCO annual meeting, the real world study (RWS) on the treatment of HCC (hepatocellular carcinoma) by the team of Professor Sun Huichuan and academician fan Jia, President Zhou Jian and Professor Sun Huichuan of Zhongshan Hospital Affiliated to Fudan University [4] was the icing on the cake.in August 2019, the United States Food and Drug Administration (FDA) has approved the combination therapy of pabolizumab and rivatinib as a breakthrough therapy for advanced unresectable HCC patients who cannot be treated locally by first-line treatment.▍ the keynote-524 trial was an open, single arm, multicenter study (ASCO Abstract 4519 nct03006926).the combination of "Wang Bao" and "Wang Bao" is of great significance for the treatment of liver cancer. It can regulate the changes of tumor associated macrophages, reverse the tumor immunosuppressive microenvironment and maintain the immune activation state. Pabolizumab has the effect of reactivating T cells, so the combination of the two drugs can achieve better results The curative effect of killing tumor.the early keynote-524 was only explored in Japanese patients with liver cancer. In order to further clarify the safety and efficacy in other ethnic groups, the enrolled population was subsequently expanded to the United States.this year, ASCO reported the clinical results of 100 patients treated with "Wang Ji" combination of first-line treatment [3]: 104 patients were enrolled in the study, and 100 patients were included in the analysis.in the 100 patients, the MOS (median overall survival time) was 22.0 months (95% CI: 20.4 months - not achieved); MPFs was 8.6 months (95% CI: 7.1-9.7 months, RECIST v1.1 per IIR); the disease control rate (DCR) was 88%.according to mrecist criteria, Orr was 46% (95% CI: 36.0% - 56.3%), including 11 cases of Cr and 35 cases of PR, and the duration of remission (DOR) was 8.6 months (95% CI: 6.9 months - not achieved).Table 2: updated data of 2020asco keynote-524 study ▍ leap-002 phase III trial leap-002 is a multicenter, randomized, double-blind phase III clinical trial. The optimal assumption of the study is that the efficacy of lovastatin plus pabolizumab in the treatment of HCC patients is better than that of the use of rivarotinib alone.750 patients are expected to be included in the study. All patients are BCLC stage C or BCLC B HCC patients who are not suitable for radical treatment and local treatment. They are randomly divided into 1:1 ratio. the experimental group was treated with rivarotinib (12mg daily for patients with body weight ≥ 60kg and 8mg daily for patients with body weight < 60kg) combined with pabolizumab (200mg every time for patients with body weight less than 60kg), while patients in the control group were treated with rivarotinib (dosage and usage the same as before) and placebo (dosage and usage the same as before), and the patients with disease progression or intolerable adverse reactions Stop taking the medicine. the longest use time of pabolizumab was 35 cycles (105 weeks). PFS and OS were the primary endpoints, while orr, DOR, DCR, AE (adverse events) and SAE (severe adverse events) were the secondary endpoints. at present, the project has been completed and is under observation and follow-up. there are 172 research centers in the world and relevant hospitals in China participate in clinical research. ▍ real world study Professor Sun Huichuan from Sun Yat Sen Hospital Affiliated to Fudan University selected two abstracts of ASCO meeting in succession at the recent ASCO annual meeting, one of which was the real world study on the unresectable / advanced primary HCC treated with lovastatin combined with PD-1 monoclonal antibody (ASCO Abstract e16610). in this study, 59 patients with advanced liver cancer were enrolled in this study. The first-line and second-line treatment with combined therapy of lovastatin and PD-1 antibody achieved 60.5% and 43.8% orr (mrecist standard), of which 43 cases (72.9%) were treated with the combined regimen as first-line treatment, and 6 cases (10.2%) achieved R0 resection [4]. Table 3: the RWS research data of sun Huichuan team of 2020asco team has promoted the development of liver cancer treatment in an all-round way, from keynote-524 trial in phase IB, leap-002 trial in phase III, and real world research in Zhongshan Hospital Affiliated to Fudan University. it is expected that lovastatin can be more widely used in the treatment of patients with liver cancer in the future, and become the gospel of patients with advanced liver cancer. in addition to liver cancer and gastric cancer, the combination of "Wang Bao" has excellent effect in many kinds of cancer, such as renal cancer, endometrial cancer, non-small cell carcinoma, head and neck squamous cell carcinoma, melanoma and urothelial carcinoma. ▍ as early as 2018, the FDA has awarded the "Wang fried" combination of breakthrough therapy in the field of renal cancer! This year, ASCO updated the results from the keynote-146 / study 111 study cohort of stage II renal cell carcinoma. the patients in the study group were given 200 mg pabolizumab intravenously every three weeks, and at the same time, 20 mg of rivatinib was orally administered once a day. at week 24, Orr was 51% (95% CI: 41-61); overall orr was 55%, PR rate was 55%; mdor was 12 months (95% CI: 9-18); MPFs was 11.7 months (95% CI: 9.4-17.7), 12-month PFS rate was 45% (95% CI: 32-57); MOS had not yet reached (95% CI: 16.7-nr), and 12-month OS rate was 77% (95% CI: 67-85) [5]. ▍ endometrial cancer in September 2019, based on the results of a single arm phase II keynote-146 / study 111 clinical trial, the combination of "Wang Bao" was approved by FDA for the treatment of patients with advanced endometrial cancer who did not have high microsatellite instability (MSI-H) or mismatch repair defect (dmmr) after systemic treatment. in March 2019, the Lancet Oncology published the interim analysis results of pabolizumab combined with rivarotinib in the treatment of advanced endometrial cancer. 54 patients were recruited in the study, 53 of them were included in the analysis, and the median follow-up time was 13.3 months; the results showed that the MPFs of patients reached 7.4 months; at the 24th week, 1 patient got Cr and 20 patients PR [6]. in 2020, the results of a phase Ib / II multicenter study on the treatment of solid tumors with the combination of "Wang Chao" were published in JCO journal. This study included 137 patients with advanced solid tumors, including 30 patients with renal cell carcinoma, 23 with endometrial cancer, 22 with squamous cell carcinoma of head and neck, 21 with melanoma, 21 with non-small cell lung cancer and 20 with urothelial carcinoma. Most of the patients (75%) accepted the treatment previously After systematic treatment. the results showed that [7]: the total orr of non-small cell lung cancer was 33%, and that of 24 week orr was 33%, including 1 case of Cr, DCR [DCR = (Cr + PR + SD) / N * 100%] was 81%, mdor was 10.9 months, MPFs was 5.9 months; total orr of renal cell carcinoma was 70%, 24 weeks orr was 63%, DCR was 97%, mdor was 20 months, MPFs was 19.8 months; the total orr of endometrial carcinoma was 52%, and the orr of 24 weeks was 52%, in which two cases achieved Cr, DCR was 96%, and MPFs was 9.7 Results: the total orr of head and neck squamous cell carcinoma was 46%, 36% at 24 weeks, 91% at DCR, 8.2 months at mdor and 4.7 months at MPFs; the total orr of melanoma was 48%, 24 weeks orr was 48%, DCR was 81%, mdor was 12.5 months, MPFs was 5.5 months; total orr of urothelial carcinoma was 25%, 24 weeks orr was 25%, DCR was 70%, MPFs was 5.4 months. Table 4: the data of "Wang Chao" combination in the treatment of multiple solid tumors! From the above clinical trials, we can see that the combination of "Wang Chao" has not only a wide participation in the field of liver cancer, gastric cancer and many kinds of cancer, but also has the therapeutic effect of clinical verification and medical recognition. at present, the treatment of advanced cancer has gradually entered the era of "targeted + immune" combination therapy. It is believed that in the near future, the combination of lovastatin and pabolizumab will continue to bring good news to Chinese patients, and the combination of "Wang Zhi" will become the "trump card" in the minds of doctors! 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 [published online ahead of print, 2020, Jun 23]. Lancet Oncol. 2020; s1470-2045 (20) 30271-0 doi:10.1016/S1470-2045 (20)30271-0[2] Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018; 391(10126):1163-1173. doi:10.1016/S0140-6736 (18)30207-1[3] A phase Ib study of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC). First Author: Andrew X. Zhu, Massachusetts General Hospital Cancer Center and Jiahui International Cancer Center, Boston, MA. ASCO 2020.[4] Sun, H.-C. (2020). Combination therapy with lenvatinib and anti-PD-1 antibodies for unresectable or advanced hepatocellular carcinoma: A real-world study, ASCO Virtual Scientific Program, American Society of Clinical Oncology.[5] Lee, C.-H. (2020). Phase II trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) for disease progression after PD-1/PD-L1 immune checkpoint inhibitor (ICI) in metastatic clear cell renal cell carcinoma (mccRCC), ASCO Virtual Scientific Program, American Society of Clinical Oncology.[6] Makker V, Rasco D, Vogelzang NJ, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20(5):711-718. doi:10.1016/S1470-2045 (19)30020-8[7] Taylor MH, Lee CH, Makker V, et al. Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. J Clin Oncol. 2020;38(11):1154-1163. doi:10.1200/JCO.19.01598