Which new drugs and programs have been approved by the FDA? Quickly onlookers~
This issue's summary
On March 27, the U.S. FDA approved duvalizumab combined with etoposide + carboplatin or cis Platinum as the first-line treatment for patients with extensive-stage small cell lung cancer;
On April 8, the US FDA approved the combination of Cornefinib and Cetuximab for the treatment of BRAF V600E mutation Positive patients with metastatic colorectal cancer who have progressed after previous treatment;
On April 15, the US FDA approved mitomycin gel asThe first drug to treat low-grade upper urothelial cancer;
On April 17, the US FDA approved the HER2-specific inhibitor Tucatinib and Trato Combination of Razumab and capecitabine for the treatment of patients with advanced HER2-positive breast cancer who cannot be resected or metastatically treated by surgery;
April 17, USA The FDA approved Pemigatinib for the treatment of locally advanced or metastatic cholangiocarcinoma that is recurrent and unresectable.
On April 22, the US FDA approved Sacituzumab govitecan-hziy for the treatment of patients with metastatic triple-negative breast cancer.
1. Duvalizumab combined with platinum-containing chemotherapy regimen for extensive useFirst-line treatment for small cell lung cancer (ES-SCLC) patients
In December 2019, Duvalizumab was approved by the National Medical Products Administration (NMPA) of China for acceptance Treatment of unresectable, stage III non-small cell lung cancer (NSCLC) patients with no disease progression after platinum-based chemotherapy and concurrent radiotherapy.
On March 27, 2020, The U.S. Food and Drug Administration (FDA) approved duvalimab (Durvalumab) combined with etoposide + carboplatin or cisplatin as ES-SCLC First-line treatment plan for patients.
SCLC is an aggressive and fast-growing type of lung cancer. Although initially highly responsive to platinum-containing chemotherapy, it will quickly relapse and progress, and subsequent treatment is lacking Effective treatment plan. SCLC patients treated with EP (etoposide combined with platinum) usually relapse within 6 months after treatment, and the median overall survival (OS) is about 10 months.
The The approval of the treatment plan is based on the results of the randomized controlled, multi-center, phase III clinical trial CASPIAN (NCT03043872). The results of the study showed that compared with the chemotherapy alone group (etoposide + carboplatin or cisplatin), Duvaliu The risk of death in the monoclonal antibody combined with chemotherapy group was significantly reduced by 27% (HR=0.73, 95%CI:0.591-0.909, p=0.0047), OS was significantly prolonged (median OS: 13.0 months vs 10.3 months). In addition, in terms of the objective response rate (ORR), the duvalimab combined with chemotherapy group was 68% (95% CI: 62%-73%), and the chemotherapy group alone was 58% (95 % CI: 52%-63%).
Duvalizumab is another immunosuppressant that has shown sustained anti-tumor effects in the treatment of ES-SCLC. The approval of the drug duvalizumab further gives SCLC patients the hope of prolonged survival.
II. Combination of Cornelfenib and Cetuximab in the treatment of BRAF V600E mutation-positive colorectal cancer patients
April 8, 2020,The US FDA approves the combination of Encorafenib and Cetuximab for the treatment of BRAF V600E mutation-positive patients with metastatic colorectal cancer (CRC) who have progressed after previous treatment . This approval is based on the results of the BEACON CRC trial, a phase III clinical trial that specifically studies previously treated patients with BRAF V600E mutation-positive, metastatic colorectal cancer.
Globally, colorectal cancer is male The third most common type of cancer, The second most common type of cancer in women. BRAF V600E mutation is one of the most common types of BRAF mutations. The risk of death in colorectal cancer patients with BRAF V600E mutation is more than twice that of wild-type BRAF.
The results of the multi-center, randomized controlled BEACON CRC clinical trial (NCT02928224) showed that the median OS of patients in the combined treatment group of Cornelfinil + Cetuximab was 8.4 months, while the control group (irinotecan+irinotecan) was 5.4 months (HR=0.52, 95%CI: 0.39-0.70; P <0.0001). The median progression-free survival (PFS) of the patients in the combined treatment group of Cornelfinil + Cetuximab was4.2 months, while the control group was only 1.5 months (HR =0.40, 95% CI: 0.31-0.52; p<0.0001).
3. The FDA approved the first drug for the treatment of low-grade urothelial cancer-mitomycin gel
On April 15, 2020, US FDA approved Mitomycin gel is the first drug for the treatment of low-grade upper urothelial carcinoma (UTUC). Mitomycin gel is an alkylating drug that can inhibit the transcription of DNA into RNA and prevent protein synthesis, thereby inhibiting the proliferation of cancer cells.
UTUC refers to the canceration of urothelial cells in the kidney or upper ureter. It is one of the most common types of bladder cancer. UTUC can block the ureter or kidney. Causes patients to develop swelling, infection and renal impairment. Although the incidence of low-grade UTUC is not high, 6000-8000 new patients are affected by low-grade UTUC every year in the United States. Low-grade UTUC is not aggressive and rarely comes from the kidneys or ureters. Spread, but often relapse after treatment.
The FDA’s approval of mitomycin gel is based on the positive results of the OLYMPUS Phase III clinical trial. The results of the study showed that Among the 71 patients with low-grade UTUC included, 41 (58%) received the weekly silkAfter treatment with schitomycin gel, complete remission was achieved, and 19 of the 41 patients (46%) who achieved complete remission remained in complete remission at 12 months.
Four. FDA approves Tucatinib for second-line treatment of HER2-positive advanced breast cancer
On April 17, 2020, US FDA approved HER2 specific inhibitor Tucatinib (Tucatinib) combined with trastuzumab and capecitabine is used to treat patients with advanced HER2-positive breast cancer that cannot be resected or metastatically treated by surgery.
The approval of tocatinib is based on data from the HER2CLIMB clinical trial. HER2CLIMB is a randomized, double-blind, placebo-controlled, positive-drug-controlled clinical trial. In patients with locally advanced unresectable or metastatic HER2-positive breast cancer, the combination regimen of tucatinib, trastuzumab and capecitabine and the regimen of trastuzumab and capecitabine Comparison.
The results of the study show that compared with trastuzumab + capecitabine regimen, tucatinib + trastuzumab + capecitabine regimen performs better Curative effect, significantly reducing the risk of disease progression or death by 46%, and the median PFS was 7.8 months vs 5.6 months (HR=0.54, 95%CI: 0.42-0.71, p<0.00001). Moreover, the combined treatment of tocatinib significantly prolonged the patient’s OS. The median OS was 21.9 months vs. 17.4 months, respectively, and the risk of death was reduced by 34% (HR=0.66, P=0.005).
Tocatinib is an oral biologically effective tyrosine kinase inhibitor (TKI), which is highly selective for HER2 and has no obvious inhibitory effect on EGFR. Tocatinib as a single drug, combination chemotherapy and other HER2 targeted drugs (such as trastuzumab) has shown significant anti-tumor activity. Previously, tocatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases. This approval makes tocatinib a treatment for HER2-positive metastasesA valuable drug supplement for sexual breast cancer.
5. The first targeted drug Pemigatinib for the treatment of recurrent and unresectable locally advanced or metastatic cholangiocarcinoma was approved
April 2020 On the 17th, US FDA approved Pemigatinib for the treatment of recurrent and unresectable locally advanced or metastatic cholangiocarcinoma. Pemigatinib is the first targeted therapy drug approved by the FDA for this indication.
Bile duct cancer is a rare cancer that occurs in the bile duct. According to its anatomical origin, it can be divided into intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma. Among them, 10%-16% of patients with intrahepatic cholangiocarcinoma will have FGFR2 gene fusion or rearrangement, which is closely related to tumor cell proliferation, migration and angiogenesis. Patients with cholangiocarcinoma are usually in the advanced stage of the disease at the time of diagnosis. Combination chemotherapy is the current standard initial treatment, but the efficacy is limited and the patient's prognosis is poor.
Pemigatinib is a fibroblast growth factor receptor (FGFR) 1/2/3 kinase inhibitor. The FDA approval is based on data from the FIGHT-202 study. FIGHT-202 (NCT02924376) is a phase II, multi-center, open-ended, single-arm study to evaluate Pemigatinib in the pastSafety and efficacy in adults (age ≥ 18 years) with locally advanced or metastatic cholangiocarcinoma who have been treated and FGFR2 gene fusion or rearrangement has been confirmed.
The results of the study showed that among the included 107 patients, the overall response rate of patients with FGFR2 gene fusion or rearrangement treated with Pemigatinib monotherapy was 36%, of which complete response was The patients accounted for 2.8%, and the patients with partial remission accounted for 33%. Of the 38 patients who responded to treatment, 24 (63%) had a response that lasted 6 months or longer, and 7 (18%) had a response that lasted 12 months or longer. The efficacy results observed in this study are clinically significant, and are beneficial for evaluating the overall benefit of tumor patients with FGFR2 gene fusion and other rearrangements.
Based on the above conclusions, PeMigatinib is approved by the FDA for the treatment of locally advanced or metastatic cholangiocarcinoma that is recurring and unresectable. This indication is approved through the accelerated approval process based on the positive results of the patient's overall response rate and duration of response.
VI. Sacituzumab govitecan-hziy was approved by the FDA for the treatment of refractory metastatic triple-negative breast cancer
On April 22, 2020, the FDA accelerated the approval of Sacituzumab govitecan-hziy is used to treat patients with metastatic triple-negative breast cancer (mTNBC).
In patients with metastatic triple-negative breast cancer who have received previous treatment and the disease has progressed, the follow-up treatment options are few and standardThe remission rate of chemotherapy is low, and the prognosis of patients is poor. Sacituzumab govitecan-hziy is a new type of antibody-drug conjugate, which combines humanized monoclonal antibody with topoisomerase I inhibitor (SN-38), humanized monoclonal antibody can target Trop-2 is a cell surface glycoprotein that is highly expressed in triple-negative breast cancer cells. Therefore, Sacituzumab govitecan-hziy can deliver high concentration of SN-38 directly to tumor cells to achieve the purpose of killing tumors.
The approval of Sacituzumab govitecan-hziy is based on the data from the clinical study of IMMU-132-01 (NCT 01631552). IMMU-132-01 is a multi-center, single-arm study that included 108 patients with metastatic triple-negative breast cancer. These patients had failed treatment with at least two other available therapies before. The main observation indicators of the study are ORR (Objective Response Rate).
The results of the study showed that the patient’s ORR was 33.3% (95% CI: 24.6-43.1), and the median duration of remission was 7.7 months (95% CI: 4.9-10.8), Sacituzumab goThe application of vitecan-hziy drugs can significantly prolong the survival of patients with refractory metastatic triple-negative breast cancer. The FDA accelerated the approval of Sacituzumab govitecan-hziy for refractory metastatic triple-negative breast cancer based on the positive results of the patient’s ORR and duration of remission in the trial.
 Yang Mengyuan, Hu Hanguang , Chen Jiaqi, et al. Progress in the treatment of BRAF-mutated advanced colorectal cancer[J]. Journal of Practical Oncology, 2019(4).
This article first appeared: the medical profession tumor Channel
The author: green Zijin