Drug Combo Beats Vemurafenib Alone for Colorectal Cancer

Published OnlineFirst February 2, 2017; DOI: 10.1158/2159-8290.CD-NB2017-013

NEWS IN BRIEF remarkable because it’s a personalized prolong PFS (Cancer Discov 2016;6: NOTED product,” commented Neelapu. 1352–65). Also, on average, patients’ cells were At the symposium, Kopetz and col- Takeda Oncology acquired ARIAD sent to Kite and returned for infusion leagues presented the results of a phase II/ Pharmaceuticals for $5.2 billion. The in 17 days, which “compares favorably III trial in which they randomly assigned Japanese company has been looking to with a lot of other CAR T-cell prod- 49 patients to receive the three-drug regi- replenish its oncology portfolio, with its ucts,” he said. “This is the shortest men and 50 patients to receive irinotecan patent on the multiple myeloma drug bort- turnaround time reported to date.” and cetuximab. All of the patients carried ezomib (Velcade) expiring this year. The Researchers now want to gain a bet- BRAF mutations, had either metastatic deal nets Takeda two key drugs: ponatinib ter understanding of how the therapy colorectal cancer or locally advanced, (Iclusig), approved for certain leukemias; works and which patients are most likely inoperable tumors, and had already had and brigatinib, an ALK inhibitor under FDA to respond to it. For example, Neelapu at least one round of chemotherapy. If review for non–small cell lung cancer. said that they want tease out the their tumors progressed during the trial, Francis Collins, MD, will continue to mechanism driving the neurologic side patients in the two-drug group could serve as the director of the NIH—at effects. They also want to understand shift to the other group. least temporarily. It remains unclear why patients who experienced a com- The median PFS for patients who whether President Donald Trump will plete or partial response subsequently received the three-drug combination formally reappoint Collins or eventu- relapsed—and why some didn’t respond was 4.4 months, versus 2 months for the ally name a successor. at all. “The intensity of the target expression patients in the irinotecan and cetuximab A new analysis reveals that the risk of does not seem to correlate with response, group. Kopetz and colleagues found dying from cervical cancer is higher at least not in our initial analysis,” he that 67% of the patients treated with than previously thought (Cancer 2017 said. –Suzanne Rose ■ all three drugs achieved disease control, Jan 23 [Epub ahead of print]). Unlike whereas only 22% of the patients who prior estimates that included women received irinotecan and cetuximab who had had a hysterectomy and were Drug Combo Beats did. The study shows that “there is therefore no longer at risk, this analysis Vemurafenib Alone for activity and clinical beneﬁ t with the included only women with a cervix. Colorectal Cancer combination of a BRAF and an EGFR The FDA greenlighted NantKwest’s inhibitor,” says Kopetz. application for a first-in-human clinical Vemurafenib (Zelboraf; Genentech) Because BRAF-mutated metastatic trial evaluating genetically modified alone hasn’t proven effective against colorectal cancer is relatively uncom- natural killer (NK) cells in patients with meta static colorectal cancer. However, mon, the trial “is an important accom- metastatic solid tumors. Researchers at combining the drug with irinotecan and plishment,” says Frank Sinicrope, MD, NantKwest in Culver City, CA, have engi- cetuximab (Erbitux; Lilly) increases pro- of the Mayo Clinic in Rochester, MN, neered these cells to express a variant of gression-free survival (PFS) in patients who wasn’t connected to the study. “It the CD16 receptor, as well as IL2; pre- with the disease, according to a study has the potential to impact clinical prac- clinically, adding these high-affinity NK presented in January at the American tice. Many oncologists will be interested cells to therapeutic antibodies boosted Society of Clinical Oncology’s 2017 in using this regimen, given the lack of antitumor immune responses. Gastrointestinal Cancers Symposium. targeted therapies for these tumors,” he Electronic cigarettes, also called Approved for treating advanced mel- says. Three serious side effects—anemia, e-cigarettes, are attracting adolescents anoma, vemurafenib targets the BRAF nausea, and neutropenia—were more who might not otherwise have started V600E mutation carried by about 7% common among patients who received using tobacco products, according to a of patients with metastatic colorectal the vemurafenib combination. However, recent study (Pediatrics 2017 Jan 23 cancer. Although vemurafenib seemed says Sinicrope, “we regard these as man- [Epub ahead of print]). Some experts like a promising option for these patients, ageable toxicities.” have thought that e-cigarettes might in a phase II study published in 2015, Kopetz and his colleagues are also be responsible for a decline in cigarette Scott Kopetz, MD, PhD, of The Uni- exploring other options for patients smoking among youth, but this first versity of Texas MD Anderson Cancer with metastatic colorectal cancer, such national analysis found that combined Center in Houston, and colleagues saw as adding a MEK inhibitor to help the e-cigarette and cigarette use among mid- no clinical beneﬁ t. BRAF inhibitor block the MAPK path- dle and high school students in 2014 was Because cancer cells compensate for way, which is often overactive in the higher than total cigarette use in 2009. the inhibition of BRAF by activating disease. The researchers will be part of Reuters reported that 22 of the world’s EGFR, the researchers tried a new regimen, the new BEACON CRC trial, which will largest drug companies will contribute adding the EGFR inhibitor cetuximab test cetuximab along with two investi- seed funding of $50 million over the and the chemotherapy drug irinotecan, gational compounds, the BRAF inhibi- next 3 years to a World Bank project to which promotes apoptosis. A phase I tor encorafenib (Array BioPharma) and fight cancer and other noncommunica- trial published in 2016 suggested that the MEK inhibitor binimetinib (Array ble diseases in poor countries. Dubbed this three-drug combination might BioPharma). –Mitch Leslie ■ Access Accelerated, the initiative was announced in Davos, Switzerland, dur- For more news on cancer research, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals. ing the World Economic Forum. org/content/early/by/section.

242 | CANCER DISCOVERYMARCH 2017 www.aacrjournals.org

Drug Combo Beats Vemurafenib Alone for Colorectal Cancer

Cancer Discov 2017;7:242. Published OnlineFirst February 2, 2017.

Updated version Access the most recent version of this article at: doi:10.1158/2159-8290.CD-NB2017-013

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