Noted This Week

November 30–December 6

Substituting adjuvant trastuzumab emtansine (T-DM1; Kadcyla; Genentech) for trastuzumab (Herceptin; Genentech) may improve outcomes for patients with early-stage HER2-positive breast cancer who have residual disease after treatment, according to findings presented at the 2018 San Antonio Breast Cancer Symposium in Texas, and simultaneously published. In the phase III KATHERINE trial, 12.2% of patients treated with T-DM1 developed invasive disease or died, whereas 88.3% had not developed invasive disease at 3 years, compared with 22.2% and 77%, respectively, of those receiving trastuzumab. T-DM1, a conjugate of trastuzumab and the anticancer drug DM1, is FDA approved for metastatic HER2-positive breast cancer.

NCI Director Ned Sharpless, MD, spoke about the importance of big data in cancer research at the 2018 American Society of Hematology (ASH) Annual Meeting in San Diego, CA. For the NCI, "the overarching goal is to create large, linked, multimodal databases that have histology and radiology and genetics and clinical outcomes, and … make them available to the research community in the most useful format possible," he said.

The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah; Novartis) elicits lasting responses in patients with relapsed/refractory leukemia and lymphoma, according to updated results of two phase II trials presented at the ASH Annual Meeting. In the ELIANA trial, 79 pediatric and young adult patients with acute lymphoblastic leukemia had an overall response rate (ORR) of 82%, and a complete response rate (CRR) of 62%. At 18 months, 66% of the complete responders were still in remission, and the overall survival (OS) rate was 70%; the median OS had not been reached. In the JULIET trial, 115 adult patients with diffuse large B-cell lymphoma had an ORR of 54% and a CRR of 40%, with a median OS of 11.1 months. At 19 months, the median duration of response had not been reached.

Also at the ASH Annual Meeting, Amgen presented positive phase I clinical data for AMG 420, a novel bispecific T-cell engager that targets BCMA. In the trial, 42 patients with relapsed/refractory multiple myeloma were treated with varying doses of the drug. In total, 13 responded, with seven complete responses, and 48% of patients experienced serious side effects; the second-highest dose (400 µg/day) elicited responses in seven out of ten patients, with six still responding at 7.5 months. AMG 420 has been granted a fast track designation by the FDA.

"We're living in an extraordinary period of innovation, particularly in this domain of CAR T-cell therapeutics, yet there are some challenges ahead [in terms of] how these T-cell therapeutics get paid for," said Joseph Alvarnas MD, of the City of Hope Comprehensive Cancer Center in Duarte, CA, while moderating a session on CAR T-cell therapies at the ASH Annual Meeting. During the session, researchers discussed their reimbursement experiences with the therapies, including difficulties they’ve encountered with Medicare payment.

GlaxoSmithKline finalized a deal to acquire Tesaro for $5.1 billion. Tesaro’s lead drug is the PARP inhibitor niraparib (Zejula) that was FDA approved in 2017 as a maintenance therapy for women with recurrent ovarian, fallopian tube, or primary peritoneal cancers, and is now being tested in lung, breast, and prostate cancers. Tesaro is also developing other anticancer drugs, including PD-1, TIM3, and LAG3 inhibitors.

Genentech announced that the FDA approved the PD-1 inhibitor atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) and chemotherapy as a first-line treatment for patients with metastatic nonsquamous non–small cell lung cancer who do not have EGFR/ALK mutations. The approval is based on the phase III IMpower150 trial, in which patients treated with the combination had a median progression-free survival of 8.5 months and a median OS of 19.2 months, compared with 7 months and 14.7 months, respectively, in patients who received bevacizumab and chemotherapy.

AbbVie will halt enrollment of a phase III trial of rovalpituzumab tesirine (Rova-T), an antibody–drug conjugate being tested as a second-line therapy for advanced small cell lung cancer. The decision was based on the TAHOE trial, in which patients treated with the drug had a shorter OS than patients who received standard topotecan chemotherapy.


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