nivolumab单药获批SCLC治疗
周末有点事情，下周撸个详细的
昨日FDA加速批准nivo单药治疗先前接受过包括一轮是含铂化疗在内的2轮及以上治疗后进展的小细胞肺癌（所以这个应该是三线了吧，好忐忑 ）。
The FDA has granted an accelerated approval to single-agent nivolumab (Opdivo) for the treatment of patients with small cell lung cancer (SCLC) with disease progression following platinum-based chemotherapy and 1 other line of therapy.
你们看把阿贵or阿宝激动的。
早先在4月份，FDA就授予该项申请优先审评资格。该项批准基于checkmate 032 的研究中小细胞肺癌亚组，文章已经发表于Lancet。
看了这个design是觉得，罗氏为了卖beva是不择手段，施贵宝为了卖ipi也是绞尽脑汁，因为ipi的毒性，所以尝试了2种剂量。
结果
安全性事件：此图不全，ipi的确增加了3-4级TRAE，但控制剂量基本还是可控。
中国临床也在进行
原文
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that Opdivo (nivolumab) received approval from the U.S. Food and Drug Administration (FDA) as the first and only Immuno-Oncology treatment option for patients with metastatic small cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy.1 Approval for this indication has been granted under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
“At Bristol-Myers Squibb, we recognize the critical need to provide patients with cancer therapies that may offer more durable responses – particularly for those living with hard-to-treat, aggressive diseases like small cell lung cancer,”2 said Sabine Maier, M.D., development lead, thoracic cancers, Bristol-Myers Squibb. “This approval builds on our heritage of bringing Immuno-Oncology therapies to patients with other types of thoracic cancers. It also reinforces our commitment to bringing transformative treatments to patients in urgent need of effective new options.”
Opdivo is associated with the following Warnings and Precautions: immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion reactions; and embryo-fetal toxicity.1 Please see the Important Safety Information section below.
This approval for Opdivo in patients with SCLC whose cancer has progressed after two or more prior lines of therapy was granted priority review from the FDA.
The approval was based on data from the SCLC cohort of the ongoing Phase 1/2 CheckMate -032 study evaluating Opdivo in patients who experienced disease progression after platinum-based chemotherapy.1 Of 109 patients receiving Opdivo after platinum-based chemotherapy and at least one other prior line of therapy, 12% (n=13/109; 95% CI: 6.5-19.5) responded to treatment based on assessment by a Blinded Independent Central Review (BICR), regardless of PD-L1 expression.1,3 Twelve patients had a partial response (11%), and one patient had a complete response (0.9%).1,3 Among these responders, the median DOR was 17.9 months (95% CI: 7.9-42.1; range: 3.0-42.1 months).3 Opdivo was discontinued in 10% of patients, and one dose was withheld in 25% of patients for an adverse reaction.1 Serious adverse reactions occurred in 45% of patients.1 The approved dosing for Opdivo in this indication is 240 milligrams administered every 2 weeks by intravenous infusion until disease progression or unacceptable toxicity.1
“While Immuno-Oncology innovations have dramatically changed how oncologists approach certain cancers, we have had limited progress for patients with small cell lung cancer,” said Leora Horn, M.D., M.Sc., associate professor of medicine, Ingram associate professor of cancer research, director of the thoracic oncology program and assistant vice chairman for faculty development, Vanderbilt University Medical Center. “Today’s approval of nivolumab is particularly exciting considering it is the first checkpoint inhibitor approved for these specific patients, and now we can finally treat this devastating disease from a different angle.”1
Small cell lung cancer is one of two main types of lung cancer and accounts for about 10% to 15% of all lung cancers.4 Small cell lung cancer is an aggressive disease, and symptoms often are not detected until the cancer is at an advanced stage.2 In the United States, about 27,000 cases of SCLC are expected to be diagnosed in 2018.5 From the time of diagnosis, five-year survival rates for extensive stage SCLC, or Stage IV, are about 2%.6
“Small cell lung cancer can be a very challenging disease, particularly for those who have already been through multiple types of treatment, as most patients relapse within a year of diagnosis,”7 said Andrea Ferris, president and chairman of LUNGevity Foundation. “This approval marks a major milestone for the patients touched by this unrelenting disease and may motivate them to pursue further treatment where there previously were no other approved options.”
Approval Based on CheckMate -032 Trial
CheckMate -032 is a Phase 1/2 multicenter, multi-cohort, open-label and ongoing trial, including 245 patients with SCLC who had experienced disease progression after platinum-based chemotherapy treated with Opdivo monotherapy.1,8 Efficacy was based on 109 patients who had experienced disease progression after platinum-based chemotherapy and at least one other prior line of therapy.1These patients received 3 mg/kg of Opdivo given by intravenous infusion over 60 minutes every 2 weeks and were included regardless of their PD-L1 status.1 Infusions were administered to patients until disease progression or unacceptable toxicity. The trial excluded patients with autoimmune disease, medical conditions requiring systemic immunosuppression, symptomatic interstitial lung disease, or untreated brain metastasis.1 Patients with treated brain metastases were eligible if neurologically stable.1
The first tumor assessments were conducted 6 weeks after the first dose and continued every 6 weeks for the first 24 weeks and every 12 weeks thereafter.1 The major efficacy outcome measures were confirmed ORR, which was further characterized by DOR, as assessed by a BICR.1 The median duration of therapy in patients treated with Opdivo in the CheckMate -032 trial was 1 month (range: 0 to 44.2+ months).1 Seventeen percent of patients received Opdivo for greater than 6 months, and 9% of patients received Opdivo for greater than one year.1
Select Safety Profile for the CheckMate -032 Trial
The safety was evaluated in 245 patients with SCLC who experienced disease progression after platinum-based chemotherapy.1 The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, pneumonitis, pleural effusion and dehydration.1 The most common adverse reactions (reported in at least 20% of patients) were fatigue (45%), decreased appetite (27%), musculoskeletal pain (25%), dyspnea (22%), nausea (22%), diarrhea (21%), constipation (20%) and cough (20%).1,9
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References
1. Opdivo Prescribing Information. Opdivo U.S. Product Information. Last Updated: August 2018. Princeton, NJ: Bristol-Myers Squibb Company.
2. National Cancer Institute. Small Cell Lung Cancer Treatment. Lung Cancer. https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq. Updated April 20, 2018. Accessed May 30, 2018.
3. Data on file. NIVO 403. Princeton, NJ: Bristol-Myers Squibb.
4. American Cancer Society. Key Statistics About Small Cell Lung Cancer. https://www.cancer.org/cancer/small-cell-lung-cancer/about/key-statistics.html. Revised January 4, 2018. Accessed May 30, 2018.
5. Decision Resources Group Epidemiology Data. Burlington, MA: Decision Resources Group.
6. American Cancer Society. Small Cell Lung Cancer Survival Rates, by Stage. https://www.cancer.org/cancer/small-cell-lung-cancer/detection-diagnosis-staging/survival-rates.html. Accessed May 30, 2018.
7. Pietanza C, Byers L, Minna J, et al. Small Cell Lung Cancer: Will Recent Progress Lead to Improved Outcomes? Clin Cancer Res.2015;21(10):2244-2255.
8. ClinicalTrials.gov. A Study of Nivolumab by Itself or Nivolumab Combined With Ipilimumab in Patients With Advanced or Metastatic Solid Tumors (CheckMate -032). https://clinicaltrials.gov/ct2/show/NCT01928394?term=NCT01928394&rank=1. Published August 23, 2013. Updated December 7, 2017. Accessed August 1, 2018.
9. Data on file. NIVO 414. Princeton, NJ: Bristol-Myers Squibb.