Expanded Multiple Myeloma Indication Highlights Week in Cancer News

Top news of the week in oncology, and cancer drug development.

Broader FDA Approval Sought for Daratumumab in Myeloma

A supplemental biologics license application has been submitted to the FDA for the use of daratumumab in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone as a treatment for patients with multiple myeloma following at least 1 prior therapy. The submission follows an FDA breakthrough therapy designation in this setting granted in July.

The FDA will decide within 60 days on whether to award the sBLA a priority review, which would mean a final approval decision would be made within 6 months. The application to expand daratumumab’s approval was based on 2 phase III trials. The phase III POLLUX trial demonstrated that combining daratumumab with lenalidomide and dexamethasone reduced the risk of disease progression by 63% versus lenalidomide and dexamethasone alone in patients with relapsed/refractory multiple myeloma.

In the phase III CASTOR trial, adding daratumumab to bortezomib and dexamethasone reduced the risk of progression or death by 61% in patients with recurrent or refractory multiple myeloma. The sBLA also included phase I data for treatment with daratumumab in combination with pomalidomide and dexamethasone following ≥2 lines of therapy.

See more: http://www.onclive.com/web-exclusives/fda-approval-sought-for-daratumumab-combos-in-multiple-myeloma

Pfizer Acquires Medivation for $14 Billion

Pfizer has announced plans to acquire the biopharmaceutical company Medivation, which is the developer of the androgen receptor inhibitor enzalutamide. Under the terms of the agreement, Pfizer will pay $81.50 per share in cash for Medivation, totaling approximately $14 billion. Both companies agreed to the transaction, which is expected to complete later this year.

In addition to enzalutamide, which is approved for prostate cancer and brings in close to $1.5 billion in revenue annually, Medivation also holds worldwide rights to the PARP inhibitor talazoparib (BMN-673), which was initially developed by BioMarin Pharmaceuticals. Prior to the acquisition, Medivation was engaged in conversations with the FDA on the development of registrational trials for talazoparib for patients with CRPC and small cell lung cancer. Pidilizumab is the third promising agent in Medivation's portfolio that was acquired by Pfizer.

The company licensed it in October 2014 from CureTech. Antitumor activity was shown for pidilizumab in studies for DLBCL and recently reported findings for pediatric patients with diffuse intrinsic pontine glioma.

See more: http://www.onclive.com/web-exclusives/pfizer-oncology-reach-expanding-with-medivation-acquisition

EMA Initiates Official Regulatory Review of Neratinib in HER2+ Breast Cancer

The European Medicines Agency has validated the marketing authorization application for neratinib as a potential extended adjuvant therapy for patients with HER2-positive early stage breast cancer following 12 months of trastuzumab.

The validation confirms the completion of the submission process and starts the formal review by the Committee for Medicinal Products for Human Use and the subsequent final approval decision by the European Commission. The application was based on findings from the phase III ExteNET study, which were published in the Lancet Oncology. In this study, extended treatment with neratinib demonstrated a 2-year disease-free survival rate of 93.9% compared with 91.6% in the placebo arm, representing a 33% improvement versus placebo (HR, 0.67; P = .009).

See more: http://www.onclive.com/web-exclusives/ema-initiates-official-regulatory-review-of-neratinib-in-her2-breast-cancer

Custirsen/Cabazitaxel Combo Misses Phase III Endpoint

Adding custirsen to cabazitaxel and prednisone in the second-line setting failed to improve overall survival in men with metastatic castration-resistant prostate cancer in the phase III AFFINITY trial. The open-label trial included 634 men with mCRPC who progressed on docetaxel. Patients were randomized to cabazitaxel plus prednisone with or without weekly custirsen.

Treatment was administered until progression, unacceptable toxicity, or the completion of 10 cycles. The safety profile for custirsen in the AFFINITY trial was similar to adverse-event reports in prior studies of the drug in mCRPC. The developer of the drug, OncoGenex, plans to submit the full study data for presentation as a late-breaking abstract at the 2016 ESMO Annual Congress in October.

Prior to this announcement, in April 2014, the combination of custirsen with docetaxel and prednisone also failed to significantly improve OS as a first-line treatment for men with mCRPC in the phase III SYNERGY trial. The median OS was 23.4 months with the addition of custirsen compared to 22.2 months with docetaxel plus prednisone alone (HR, 0.93; P = .207).

See more: http://www.onclive.com/web-exclusives/custirsen-combo-falls-short-in-phase-iii-mcrpc-trial

NICE Hands Down 3 No's and a Yes

The National Institute for Health and Care Excellence recommended crizotinib for the first-line treatment of patients with advanced, ALK-positive non-small cell lung cancer. In its recommendation, Britain’s healthcare cost watchdog noted that chemotherapy was the only previously available treatment option for patients in this setting. During its initial review of crizotinib, NICE determined that the drug did not meet its cost-effectiveness standards; however, Pfizer offered a further discount that persuaded NICE to offer new draft guidance recommending the drug.

Other drugs did not fare so well in recent NICE decisions. NICE has recommended removing 3 drugs currently available from the UK’s Cancer Drugs Fund for not being cost effective. The drugs include everolimus for treating advanced breast cancer after endocrine therapy, ibrutinib for treating relapsed or refractory mantle cell lymphoma, and sorafenib for treating advanced hepatocellular carcinoma.

See more on crizotinib: https://www.nice.org.uk/news/article/nice-recommends-crizotinib-first-pill-for-lung-cancer