Published OnlineFirst April 20, 2015; DOI: 10.1158/2159-8290.CD-NB2015-055

NEWS IN BRIEF PEOPLE

Dirk Douglass

José Baselga, MD, PhD, physician-inchief and chief medical officer at Memorial Sloan Kettering Cancer Center in New York, NY, was inaugurated as president of the American Association for Cancer Research (AACR) in April at the organization’s annual meeting in Philadelphia, PA. He will serve a 1-year term, succeeding Carlos Arteaga, MD. Baselga’s research focuses on the development of molecularly targeted agents to treat cancer. His work helped lead to the development and approval of the anti-HER2 monoclonal antibodies trastuzumab (Herceptin) and pertuzumab (Perjeta). He is an editor-in-chief of Cancer Discovery. Mario R. Capecchi, PhD, distinguished professor of biology and human genetics at the University of Utah School of Medicine in Salt Lake City, and an investigator at that city’s Huntsman Cancer Institute, received the AACR Award for Lifetime Achievement in Cancer Research at the organization’s annual meeting. He is best known for discovering how to genetically engineer mice in which a specific gene is deleted, work that proved vital in studying mutations common in cancer—and that earned him the Nobel Prize in physiology or medicine in 2007. Also at the AACR meeting, Donald S. Coffey, PhD, distinguished professor of urology at Johns Hopkins School of Medicine in Baltimore, MD, received the Margaret Foti Award for Leadership and Extraordinary Achievement in Cancer Research. Coffey’s studies of the structure of cell nuclei led to the discovery of the nuclear matrix. Known for his dedication to mentoring young investigators, Coffey has been a passionate advocate for increasing research funding.

568 | CANCER DISCOVERYJUNE 2015

Pembrolizumab Superior to Ipilimumab in Melanoma In the first randomized trial to compare FDA-approved immune checkpoint inhibitors as first-line therapy for patients with advanced melanoma, pembrolizumab (Keytruda; Merck) yielded significantly better treatment outcomes than ipilimumab (Yervoy; Bristol-Myers Squibb) for all endpoints studied. The findings from the study, the phase III KEYNOTE-006 trial, were presented at the American Association for Cancer Research Annual Meeting 2015, held April 18–22 in Philadelphia, PA. “We think these data should change the paradigm of treatment for these patients,” said Antoni Ribas, MD, PhD, professor of hematology and oncology and director of the Tumor Immunology Program Area at the University of California, Los Angeles, Jonsson Comprehensive Cancer Center. Ribas presented the results, which were simultaneously published in The New England Journal of Medicine (N Engl J Med 2015 Apr 19 [Epub ahead of print]). Currently, ipilimumab, a CTLA-4 inhibitor, is the standard first-line therapy for patients with metastatic melanoma. Pembrolizumab, a PD-1– blocking antibody, is approved for use in patients who no longer respond to ipilimumab or BRAF inhibitors. Researchers randomly assigned 834 patients with metastatic melanoma, 66% of whom had not received therapy previously, to receive pembrolizumab every 2 weeks (at a dose of 10 mg/kg), pembrolizumab every 3 weeks (at 10 mg/kg), or four doses of ipilimumab (at 3 mg/kg) every 3 weeks. They assessed treatment responses after 12 weeks and at every 6 weeks thereafter. Six months after the start of treatment, estimated progression-free survival (PFS) rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab. Median estimates of PFS were 5.5 months, 4.1 months, and 2.8 months respectively. After 12 months, estimated overall survival (OS) rates were 74.1%, 68.4%, and 58.2% respectively; median OS was not reached in any of the

groups. The overall response rate for the pembrolizumab group was 33%, compared with 12% for the ipilimumab group, and fewer patients in the pembrolizumab group experienced side effects (12%) compared with the ipilimumab group (20%), said Ribas. Based on the statistically significant and clinically meaningful improvements in PFS and OS with pembrolizumab, Merck stopped the clinical trial in March. In addition, Ribas said that outcomes with pembrolizumab were superior to ipilimumab in most subgroups of patients, except for OS in those with PD-L1–negative tumors, where the sample size was too small to draw definitive conclusions. Only 18% of patients in the trial had PD-L1–negative tumors. “This is now expected to change the treatment landscape for melanoma,” said Suzanne Topalian, MD, director of the melanoma program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, MD, who moderated the press conference at which the findings were presented. “This is a very high-impact trial.” “It is amazing that single-agent checkpoint blockade [with pembrolizumab] gives these responses in melanoma,” echoed Ribas. “But the reality is that two thirds of the patients do not respond, and we have to do something about that.” He said that researchers will try combining pembrolizumab with other treatments, such as targeted therapies, chemotherapy, and radiation, in an effort to boost response rates. Despite the favorable results for pembrolizumab, Ribas said he will not stop using ipilimumab, as it provides durable responses in some patients. Also, some studies have shown that combining ipilimumab with a PD-1 inhibitor yields an even greater response than using either on its own. ■

Stratifying Prostate Patients for Olaparib Results from the phase II TOPARPA clinical trial show durable antitumor activity with the PARP inhibitor olaparib (Lynparza; AstraZeneca) among a subset of patients with

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Published OnlineFirst April 20, 2015; DOI: 10.1158/2159-8290.CD-NB2015-055

Pembrolizumab Superior to Ipilimumab in Melanoma Cancer Discovery 2015;5:568. Published OnlineFirst April 20, 2015.

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Pembrolizumab superior to ipilimumab in melanoma.

In the first randomized trial to compare FDA-approved immune checkpoint inhibitors as first-line therapy for patients with advanced melanoma, pembroli...
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