Regorafenib Approved for Liver Cancer

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nEws In BRIEF to having options. Apolo points out the drug carries a black-box warning notEd that clinical trial results in other about potentially severe liver toxicity—a tumors and early results in bladder chief reason why clinicians have been The U.s. Preventive services Task Force cancer studies seem to indicate that the slow to evaluate it in HCC, says Nevena recommended against screening for drugs may be more effective in combina- Damjanov, MD, director of gastroin- thyroid cancer in asymptomatic adults . tion. “We know the response rates range testinal oncology at Penn Presbyterian The federal oversight group found inad- from about 15% to 20% when these Medical Center in Philadelphia, PA. equate evidence that population-based agents are used as monotherapy, but Extensive cirrhosis often underlies or targeted screening could decrease we’re seeing even higher response rates advanced, inoperable HCC, Damjanov mortality rates (JAMA 2017;317:1888– 903) . They noted that “screening that in combination clinical trials,” she says. explains, so with regorafenib, “physi- results in the identification of indolent “I think that’s really exciting.” cians face the diffi cult situation of try- thyroid cancers, and treatment of those Because all fi ve drugs inhibit PD-1 ing to shrink tumors with a therapy that overdiagnosed cancers, may increase or PD-L1, and seem similarly effective, could result in the patient’s already poor the risk of patient harms .” Apolo recommends enrolling patients liver function deteriorating still faster.” in an appropriate clinical trial. “If you Recruitment for the phase III study nearly one third of 222 drugs approved by the FDA from 2001 through 2010 can possibly treat someone with these (RESORCE) on which the FDA based its were affected by postmarket safety agents under a clinical trial, it just adds decision took time, she adds, because events—withdrawal, boxed warnings, to the body of knowledge,” she says. “patients had to have been able to or agency announcements about new The advice speaks to the importance tolerate sorafenib fi rst, long enough to risks—a median of 4 .2 years later (JAMA of continuing to study drugs even experience disease progression—and 2017;317:1854–63) . Eleven cancer ther- after they receive the FDA’s go-ahead. the side effects of sorafenib are not apies were among the 71 affected drugs, Earlier this month, Roche announced always easy to manage.” including cetuximab (Erbitux; Eli Lilly), that atezolizumab failed to show an RESORCE investigators reported that lenalidomide (Revlimid; Celgene), and increase in overall survival compared among 573 patients randomly assigned sunitinib (Sutent; Pfizer) . with chemotherapy in a phase III to receive regorafenib or placebo, the The University of nebraska’s Fred and follow-up study, data the FDA will median overall survival was 10.6 months Pamela Buffett Cancer Center in review when considering full approval. for those given the drug, and 7.8 months Omaha got a new $323 million building . Avelumab and durvalumab will face in the control arm (Lancet 2017;389:56– Key features include a 10-story, 98-lab- similar scrutiny. Because they were 66). The median progression-free sur- oratory research tower, as well as a granted accelerated approval, the vival was 3.1 months versus 1.5 months, sanctuary for patients, their families, FDA requires their manufacturers to and the objective response rates were and staff . The center opened to patients conduct additional studies to confi rm 11% versus 4%. in early June . a clinical benefi t. David– Shultz n As with sorafenib, patients on rego- At New York, NY’s Memorial Sloan rafenib experienced a slew of side effects, Kettering Cancer Center, researchers Regorafenib Approved including diarrhea, nausea, hypertension, established a prospective clinical fatigue, and hand–foot skin reaction. sequencing initiative to reveal the for Liver Cancer Having this drug as a second-line treat- mutational landscape of metastatic The FDA recently expanded label ment for HCC is not unlike “treating an cancer by molecularly profiling more indications for regorafenib (Stivarga; ulcer that hasn’t responded to Zantac than 10,000 patients . Their compre- Bayer) to include treating patients with with Tagamet instead,” Damjanov hensive assay, MSK-IMPACT, helped advanced hepatocellular carcinoma observes. “If possible, you’d rather try pinpoint clinically relevant somatic mutations, novel noncoding alterations, (HCC) whose disease has progressed on something completely different.” and mutational signatures shared by the standard of care, sorafenib (Nexavar; Even so, the survival benefi t seen common and rare tumor types . Bayer). Until now, these patients have with regorafenib makes it “a big deal, had no other treatment options. This especially considering that HCC still A report from the American Cancer approval also marks the first new very much lags behind other cancers Society estimates that 20% of cancers therapy for liver cancer in a decade. in terms of good therapeutic options,” could be prevented (see “Cancer Prevention & Early Detection Facts & Regorafenib and sorafenib primarily Damjanov says. She hopes immune Figures 2017–2018,” available at www . block angiogenesis; each targets a slightly checkpoint inhibitors will come to the cancer .org) . The associated suffering different combination of the RAF, fore in this diffi cult-to-treat disease, and death could be avoided by “more VEGFR, and PDGFR families. Between and is awaiting results from a phase III systematic efforts to reduce tobacco 2012 and 2013, regorafenib garnered trial comparing nivolumab (Opdivo; use and obesity, improve diet, and its fi rst agency nods to treat metastatic Bristol-Myers Squibb) with sorafenib increase physical activity and the use colorectal cancer and gastrointestinal as first-line therapy for advanced of established screening tests,” the stromal tumors, respectively. However, HCC. –Alissa Poh n authors write .

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660 | CANCER DISCOVERY JUly 2017 www.aacrjournals.org

Cancer Discov 2017;7:660.

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