Fourth-Line Treatment Approved for Gastrointestinal Tumor

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News From the Food and Drug Administration

Fourth-Line Treatment Approved epithelial transition (MET) exon 14 skipping. cancer (NSCLC). For adults or pediatric For Gastrointestinal Tumor The FDA noted that MET exon 14 skipping patients aged 12 years or older, it’s indi- The kinase inhibitor ripretinib has received is a critical event in cancer metastasis, and cated for RET-altered advanced or meta- approval as a fourth-line treatment for adults that it occurs in about 3% to 4% of patients static medullary thyroid cancer (MTC) that with advanced gastrointestinal stromal tu- with lung cancer. The agency also approved requires systemic therapy and for advanced mor (GIST) who already have been treated the FoundationOne CDx assay diagnostic or metastatic thyroid cancer with a RET with 3 or more kinase inhibitors. test, which can detect genetic alterations alteration that requires systemic therapy An estimated 4000 to 6000 adults are that lead to MET exon 14 skipping. and doesn’t respond to or isn’t appropriate diagnosed with a GIST each year, according for radioactive iodine (RAI) therapy. The to the FDA. “Despite the progress that has drug’s list price reportedly is $20 600 for been made over the past 20 years in devel- a 30-day supply. oping treatments for GIST, including four In a clinical trial, the FDA reported that FDA-approved targeted therapies…some among patients with NSCLC, 105 had patients don’t respond to treatment and received prior platinum chemotherapy and their tumors continue to progress,” Richard 39 had received no treatment. Among Pazdur, MD, director of the FDA’s Oncology treated patients, the overall response rate Center of Excellence, said in a statement. was 64%; among 81% of those patients, According to the agency, the drug’s treatment response lasted for at least 6 approval was based on a clinical trial involv- months. Among treatment-naive patients, ing 129 patients who previously were 84% responded; for 58% of them the treated with imatinib, sunitinib, and rego- response lasted 6 months or longer. rafenib. The participants were randomized Among 143 patients aged 12 years or to receive ripretinib or placebo once daily in older with MTC, some had been treated with 28-day cycles to determine progression- cabozantinib, vandetanib, or both but other free survival (PFS). On average, PFS was others had received no prior treatment. The Accelerated approval was based on a 6.3 months in the treatment group com- 55 previously treated patients had a 69% re- phase 2 clinical trial involving 97 patients, pared with 1 month in the placebo group. sponse rate, with 76% of those patients hav- according to a statement from Novartis, the Median overall survival was 15.1 months ing a response that lasted at least 6 months. drug’s manufacturer. Among patients among treated patients compared with 6.6 Among 88 patients with no prior therapy, with no prior treatment, the response rate months among patients in the placebo 73% responded. For 61% of those patients, was 68% and the median duration of group, according to the drug’s manufac- the response lasted 6 months or longer. response was 12.6 months. In comparison, turer, Deciphera Pharmaceuticals Inc. The trial also enrolled 27 patients with 41% of patients who were previously Common adverse events included alo- MTC that was RAI-refractory,if RAI had been treated responded to capmatinib and their pecia, fatigue, nausea, abdominal pain, appropriate for them. Among 19 patients median duration of response was 9.7 constipation, myalgia, and palmar-plantar who received RAI and another systemic months. The drug reportedly will cost erythrodysesthesia syndrome. Serious therapy, 79% responded; 87% of those pa- $17 950 for a 28-day supply. adverse events included skin cancer, tients had a response lasting at least 6 Common adverse events included pe- hypertension, and cardiac dysfunction months. Among 8 patients who received ripheral edema, nausea, vomiting, and dys- manifested as ejection fraction decrease. no treatment other than RAI, 100% re- pnea. Capmatinib, marketed as Tabrecta, Marketed as Qinlock, a 1-month supply sponded, including 75% whose response may also cause serious adverse events in- reportedly will cost $32 000. lasted 6 months or longer. cluding interstitial lung disease. Marketed as Retevmo, selpercatinib Targeted Therapy and Diagnostic Test can cause serious adverse events including for Non–Small Cell Lung Cancer New Drug Is a Triple Threat Against hepatotoxicity, elevated blood pressure, TheFDAhasapprovedatargetedtherapyfor RET-Altered Cancer QT prolongation, bleeding, and allergic certain adults with metastatic non–small cell The first drug indicated for patients with 3 reactions. Common adverse events in- lung cancer (NSCLC) as well as an in vitro di- typesofcancer,allofwhichhaveaspecificge- cluded elevated liver enzymes, increased agnostic test to detect genetic alterations in netic alteration, has received FDA approval. blood glucose, decreased white blood their cancer. Selpercatinib is a kinase inhibitor that cells, and decreased albumin or calcium Capmatinib is a kinase inhibitor that’s selectively targets RET gene alterations. in the blood. − Rebecca Voelker, MSJ indicated for adults who have NSCLC with The drug is indicated for adults with Note: Source references are available through alterations that lead to mesenchymal- RET-altered metastatic non–small cell lung embedded hyperlinks in the article text online.

2364 JAMA June 16, 2020 Volume 323, Number 23 (Reprinted) jama.com

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