Treatment Advances Highlight Week in Cancer News
Top news of the week in oncology drug development.
FDA Approves Eribulin for Advanced Liposarcoma
The FDA approved eribulin mesylate as a treatment for patients with advanced or unresectable liposarcoma following prior treatment with an anthracycline-based chemotherapy, based on an improvement in overall survival in a phase III study.
In 143 patients with liposarcoma, the microtubule dynamics inhibitor eribulin demonstrated a median OS of 15.6 months compared with 8.4 months in those who received dacarbazine (HR, 0.51; 95% CI, 0.35-0.75). Median progression-free survival with eribulin was 2.9 versus 1.7 months with dacarbazine (HR, 0.52; 95% CI, 0.35-0.78). Eribulin is the first drug approved for patients with liposarcoma based on an improvement in survival.
In the full study that was instrumental in the approval, 309 patients were also enrolled with leiomyosarcoma; however, eribulin was not effective in this group. In patients with leiomyosarcoma, median OS was 12.8 months with eribulin versus 12.3 months with dacarbazine (HR, 0.90) and median PFS was 2.2 versus 2.6 months, in the eribulin and dacarbazine arms, respectively (HR, 1.05).
Olaparib Receives Breakthrough Designation for mCRPC
Olaparib received an FDA breakthrough therapy designation as a treatment for patients with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer in those who have received a prior taxane-based chemotherapy and at least either hormonal agent enzalutamide or abiraterone acetate.
The designation, which will accelerate the development and review of the first-in-class oral PARP inhibitor, is based on data from the phase II TOPARP-A trial that demonstrated that olaparib monotherapy had an overall response rate of nearly 90% in a biomarker-defined subgroup of patients who had DNA-repair defects.
In the 49 evaluable patients who received at least one dose of olaparib, ORR was 33% (n = 16). At a median follow-up of 14.4 months, median OS was 10.1 months. In 14 patients who tested positive for a BRCA2 or ATM alteration, the outcomes were far superior compared with the rest of the patients.
Radiographic progression-free survival was a median of 9.8 months in the biomarker-positive group versus 2.7 months in the negative arm (P <.001). Median OS was 13.8 months in the positive group versus 7.5 months in the biomarker-negative group (P = .05). Established prognostic factors were balanced between the two groups.
Nivolumab Improves OS in Head and Neck Cancer
Nivolumab improved overall survival versus investigator's choice of therapy for patients with platinum-refractory squamous cell carcinoma of the head and neck in the phase III CheckMate-141 trial.
The study was stopped early after an independent monitoring panel determined the primary endpoint of improvement in OS was met with the anti—PD-1 agent versus the investigator's choice of cetuximab, methotrexate, or docetaxel. Eligible patients in the chemotherapy arm will be able to cross over to receive nivolumab. Findings from the study are being discussed with the FDA and other health authorities.
The positive findings from CheckMate-141 join an ever-growing collection of data supporting PD-1 inhibition across types of cancer. Following an impressive early demonstration of efficacy for nivolumab at the 2012 ASCO Annual Meeting, the agent has gained more than a half dozen indications.
At this point there is limited data for nivolumab in head and neck cancer, as the developer, BMS, decided to omit early phase development and skip directly to phase III testing. The results from the CheckMate-141 trial are likely to be presented during the 2016 ASCO Annual Meeting.
Venetoclax Gets Breakthrough Designation for AML
Venetoclax received an FDA breakthrough therapy designation for use in combination with hypomethylating agents in treatment-naïve patients with acute myeloid leukemia who are not eligible for standard high-dose induction treatment.
The designation, which will expedite the development and review of the combination in AML, is based on data from a small early-stage trial in which over 70% of untreated patients with AML had clinical responses to combination venetoclax therapy. In a phase Ib study, venetoclax was combined with the hypomethylating agents decitabine or azacitidine in 22 untreated patients with AML.
Of the 19 patients evaluable, 75% of those who received venetoclax plus decitabine experienced a response. At the 400-mg venetoclax dose, 2 patients achieved complete remission and 1 patient had a CR with incomplete marrow recovery.
There were 5 CRi’s and 1 partial response at the 800-mg venetoclax dose. In the venetoclax plus azacitidine arm, the ORR was 70%. There was 1 CR and 2 CRi’s with 400 mg of venetoclax. At the higher dose, there were 2 CRs, 1 CRi, and 1 PR.
Cabozantinib Improves OS, Receives Priority Review for RCC
The FDA granted a priority review designation to cabozantinib as a treatment for patients with advanced renal cell carcinoma following progression on one prior therapy. The application for cabozantinib was based on findings from the 658-patient phase III METEOR trial, in which cabozantinib demonstrated a 42% reduction in the risk of progression or death compared with everolimus in patients with advanced RCC.
After a minimum of 11 months of follow-up, median progression-free survival with cabozantinib was 7.4 months compared with 3.8 months with everolimus (HR, 0.58; P <.001). Data for cabozantinib was submitted on a rolling basis, under the breakthrough therapy program. Under the Prescription Drug User Fee Act, the agency is scheduled to make a decision on the application by June 22, 2016
See more on the FDA submission http://www.onclive.com/web-exclusives/fda-grants-cabozantinib-priority-review-for-rcc
A second interim analysis of the study conducted after the data were submitted showed that cabozantinib also improved overall survival. Although data are not yet available, a 5-month benefit in OS was required in order to demonstrate statistical significance. These new data will also be submitted to the FDA and are being prepared for presentation at an upcoming conference.