Top developments from the last week in cancer treatment.
Top developments from the last week in cancer treatment.
Daratumumab Receives Priority Review Designations for Myeloma
The FDA recently assigned a priority review designation to daratumumab as a treatment for patients with multiple myeloma either following at least 3 lines of therapy, including both a proteasome inhibitor and an immunomodulatory agent, or in those who are double refractory to a proteasome inhibitor and an IMiD. The priority review was based on data from the phase II MMY2002 (SIRIUS) study that were presented at the 2015 ASCO Annual Meeting.
In this trial, daratumumab demonstrated a 65% one-year overall survival rate and a 29.2% objective response rate in heavily pretreated patients with double refractory multiple myeloma. Responses to daratumumab consisted of stringent complete responses (n = 3; 2.8%), very good partial responses (n = 10; 9.4%), and partial responses (n = 18; 17%). The median duration of response was 7.4 months. After a median follow-up of 9.4 months, 45.2% of patients remained on therapy.
The median progression-free survival was 3.7 months. The FDA plans to make a decision on the biologics license application for daratumumab within 6 months, placing a decision on March 9, 2016. The priority review follows a breakthrough therapy designation for daratumumab that was granted by the FDA in May 2013.
Elotuzumab Granted Priority Review for Myeloma
The FDA recently granted elotuzumab a priority review for use in combination therapy in patients with multiple myeloma following the failure of one or more prior therapies. A separate regulatory filing for the same indication was accepted and given an accelerated review by the European Medicines Agency in late July. The FDA and EMA reviews will both be based primarily on data from the phase III ELOQUENT-2 trial, with supporting data coming from the phase II study CA204-009.
At a median follow-up of 2 years, PFS with the elotuzumab regimen was 19.4 months versus 14.9 months with lenalidomide and dexamethasone alone (HR, 0.70; P <.001). The 1-year PFS for the elotuzumab versus control arm was 68% versus 57%, respectively, with the difference in 2-year PFS rates increasing to 41% versus 27%. Under this review the deadline for a decision on elotuzumab will be set for March 2016. Prior to this, elotuzumab received a breakthrough therapy designation from the FDA in May 2014 for use in combination with lenalidomide and dexamethasone for patients with multiple myeloma following one or more prior therapies.
Nivolumab Given Priority Review, Breakthrough Designation in NSCLC
Nivolumab received an FDA priority review designation for patients with previously treated nonsquamous non­—small cell lung cancer, according to the developer of the PD-1 inhibitor, Bristol-Myers Squibb (BMS). Under the expedited process, the FDA’s decision deadline is January 2, 2016. The FDA simultaneously granted nivolumab a breakthrough therapy designation in this setting.
The priority and breakthrough designations are based on data from the phase III CheckMate-057 trial, in which second-line nivolumab reduced the risk of death by 27% versus docetaxel in patients with nonsquamous NSCLC, including a 60% risk reduction among patients with the highest levels of PD-L1 expression. Across the full population, the median overall survival was 12.2 months with nivolumab versus 9.4 months with docetaxel (HR, 0.73; P = .00155), with a 1-year OS of 50.5% versus 39.0%, respectively. The objective response rate was 19% with the PD-1 inhibitor compared with 12% with chemotherapy (odds Ratio = 1.72; P = .0246). Nivolumab was previously approved in March 2015 for patients with squamous cell NSCLC who have progressed on or after platinum-based chemotherapy.
Aprepitant's CINV Indication Expanded
The FDA has approved aprepitant capsules in combination with other antiemetic agents for the prevention of acute and delayed nausea and vomiting in patients aged 12 to 17 and for those under the age of 12 who weigh at least 30 kg who are receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy. The extension to the aprepitant indication was based on findings from a phase III clinical trial that examined aprepitant plus ondansetron compared with placebo and ondansetron.
The study enrolled 302 patients between the age of 6 months and 17 years. In those between the age of 12 and 17 or under 12 and at least 30 kg (n = 132), an acute or delayed complete response, defined as no vomiting or retching, was achieved for 34.9% of patients treated with the combination versus 13% with ondansetron monotherapy. A CR in the delay phase, defined as 25 to 120 hours following the initiation of chemotherapy, was experienced by 49.2% of patients treated with the aprepitant/ondansetron combination compared with 18.8% with ondansetron alone.
In the first 24 hours following treatment (acute phase), 55.6% of patients treated with the combination had a CR versus 37.7% with ondansetron alone. For patients under the age of 12 who weighed less than 30 kg, an appropriate commercially available dose of aprepitant is not yet available. In the phase III study, an investigational powder for suspension formulation was examined but an application for this formulation is still pending.
Panobinostat Approved in Europe for Myeloma
The European Commission has approved panobinostat in combination with bortezomib and dexamethasone for adult patients with relapsed/refractory multiple myeloma following prior treatment with bortezomib and an immunomodulatory agent. The decision, which was based on a subanalysis of the phase III PANORAMA-1 trial, makes panobinostat the first HDAC inhibitor to gain approval in the European Union. In the pivotal trial, the addition of panobinostat to bortezomib and dexamethasone improved progression-free survival by 7.8 months in a subgroup of 147 patients. Panobinostat is approved in the United States and Japan for similar indications in previously treated multiple myeloma.
The median PFS was 12.5 months in patients treated with panobinostat versus 4.7 months with placebo (HR, 0.47). Additionally, the panobinostat combination demonstrated a higher overall response rate compared with placebo (58.9% vs 39.2%). The complete response or near CR rate with panobinostat was 21.9% compared with 8.1% for placebo. The FDA approved panobinostat in February 2015.
Dabrafenib/Trametinib Combo Approved in Europe for Melanoma
The European Commission has approved the combination of dabrafenib plus trametinib for the treatment of patients with unresectable or metastatic BRAF V600—positive melanoma. The approval is based on results from the phase III COMBI-d and COMBI-v studies, in which BRAF/MEK inhibition with dabrafenib/trametinib improved overall survival versus single-agent BRAF inhibition, which is the current standard of care in Europe.
The combination of dabrafenib and trametinib demonstrated a median OS of 25.1 months compared with 18.7 months with dabrafenib alone (HR, 0.71; P = .011). The 2-year OS rate with the combination was 51% versus 42% with the single-agent. Median PFS was 11.0 months with the combination compared with 8.8 months in the control arm (HR, 0.67; P <.001). ORR was 69% versus 53%, for the combination and single-agent, respectively. The complete response rate was 16% in the combination arm compared with 13% for dabrafenib. Duration of response was 12.9 and 10.6 months in the combination and monotherapy arms, respectively.