Recent advances and updates in oncology and cancer drug development.
FDA Updates Ibrutinib CLL/SLL Label
The FDA has expanded the label of ibrutinib to include overall survival results in treatment-naive patients with chronic lymphocytic leukemia, as well as outcomes with the BTK inhibitor when combined with bendamustine and rituximab in relapsed/refractory patients with CLL. Ibrutinib is now also approved for the treatment of patients with small lymphocytic lymphoma, regardless of whether or not they harbor a 17p deletion.
The survival benefit with frontline ibrutinib was demonstrated in the phase III RESONATE-2 trial, in which the agent reduced the risk of death by 56% versus chlorambucil (HR, 0.44; 95% CI, 0.21-0.92). At a median follow-up of 18.4 months, the median PFS was not yet reached with ibrutinib versus 19 months with chlorambucil (P <.0001). By independent review, the objective response rate was 86% with ibrutinib versus 35.3% with chlorambucil.
The ibrutinib plus BR data were from the phase III HELIOS trial, in which the triplet reduced the risk of disease progression or death by 80% versus BR alone (HR, 0.20; 95% CI, 0.15-0.28; P <.0001). At a median follow-up of 17.2 months, PFS with ibrutinib was not yet reached, as compared with 13.3 months for patients receiving BR alone. ORR was 82.7% in the ibrutinib arm versus 67.8% in the control group (P <.0001).
FDA Grants Olaratumab Priority Review for STS
The FDA has granted olaratumab a priority review for use in combination with doxorubicin for the treatment of patients with advanced soft tissue sarcoma who are not good candidates for radiotherapy or surgery.
The biologics license application for olaratumab was based on data from the phase II JGDG trial, in which combining olaratumab with doxorubicin reduced the risk of death by 54% versus doxorubicin alone in patients with STS (HR, 0.46; 95% CI, 0.30-0.71; P = .0003). Median progression-free survival was 6.6 versus 4.1 months, with olaratumab plus doxorubicin versus doxorubicin alone, respectively.
Median OS was 26.5 months with the combination versus 14.7 months with doxorubicin alone. ORR was 18.2% in the combination arm compared with 11.9% in the doxorubicin arm (P = .34). The FDA previously granted olaratumab a breakthrough therapy designation in STS. Under the priority designation, the FDA will review the BLA for olaratumab within 6 months, compared with the standard 10-month review.
Blinatumomab Granted Priority Review for Pediatric ALL
The FDA has granted a priority review to an application for the expanded approval of blinatumomab, which includes the treatment of pediatric and adolescent patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia. The supplemental biologics license application was based on data from a single-arm phase I/II trial, known as study 205, which met its primary phase II endpoint of complete remission within the first 2 cycles of blinatumomab.
All patients in the trial have completed therapy and are being observed for long-term outcomes. The data are being submitted for publication, but have not yet been reported. Following a breakthrough therapy designation in July 2014, the FDA granted blinatumomab an accelerated approval for adult patients in this setting in December 2014, based on phase II data demonstrating strong clinical activity with the agent. The priority review program provides an expedited approval process for treatments that provide a substantial benefit over current options. The FDA is scheduled to make its final decision by September 1, 2016.
Regorafenib Improves OS in Phase III HCC Study
Regorafenib improved overall survival versus best supportive care in patients with unresectable hepatocellular carcinoma who progressed after receiving sorafenib, according to findings from the phase III RESORCE trial. The safety profile for the multitargeted TKI was comparable to previously reported outcomes, according to Bayer, the manufacturer of the drug.
This is the first agent to demonstrate efficacy in a phase III in the second-line setting for patients with HCC. In previously published phase II data, the median OS was 13.8 months with regorafenib and the median time to progression was 4.3 months. The disease control rate was 72%. The most frequent grade ≥3 AEs were hand-foot skin reaction, diarrhea, fatigue, and hypertension. Bayer plans to present the full results from the trial at an upcoming scientific meeting.
Clovis Halts Rociletinib Research in NSCLC
Clovis has stopped clinical development of rociletinib, its once promising EGFR inhibitor for the treatment of patients with EGFR T790M—mutated non–small cell lung cancer. In a statement, the company reported that it had been notified by the FDA that it would receive a complete response letter on or before the scheduled PDUFA date of June 28, 2016. Receiving such correspondence means that the FDA is not approving a new drug application based on the available data.
Clovis has terminated enrollment in all ongoing rociletinib studies, including the phase III TIGER-3 trial, and has withdrawn its application for regulatory approval in the European Union. Rociletinib will continue to be provided to patients whose clinicians recommend continuing therapy, according to Clovis.
This final chapter in the rociletinib saga follows a series of negative developments for the drug, including updated data revealing lower response rates than initially reported, a negative vote from the FDA’s ODAC, and FDA approval of rociletinib’s main competitor in the setting, osimertinib.
Eribulin Approved in Europe for Soft Tissue Sarcoma
The European Commission has approved eribulin mesylate as a treatment for patients with advanced or unresectable liposarcoma following anthracycline-based chemotherapy, based on data from the pivotal phase III trial, Study 309. In the trial, the microtubule dynamics inhibitor eribulin demonstrated a median overall survival of 15.6 months compared with 8.4 months in patients who received dacarbazine (HR, 0.511; 95% CI, 0.346-0.753; P = .0006) in a cohort of 143 patients with liposarcoma.
Median progression-free survival in the group was 2.9 months with eribulin versus 1.7 months with dacarbazine (HR, 0.52; 95% CI, 0.35-0.78). Across the full study, median OS with eribulin was 13.5 months compared with 11.5 months for dacarbazine, representing a >23% reduction in the risk of death (HR, 0.768; 95% CI 0.618-0.954; P = .017).
Median PFS was 2.6 months in both arms of the study across the full population (HR, 0.877; 95% CI, 0.710-1.085; P = .229). The 12-week PFS rate was 33% with eribulin and 28.6% with dacarbazine; however, this difference was not deemed statistically significant (odds ratio = 1.3; P = .253).