Novel Leukemia Therapies Highlight Week in Cancer News
Recent advances and updates in oncology and cancer drug development.
OS Longer in BRCA-Mutated Ovarian Cancer
Patients with advanced ovarian cancer harboring mutations in homologous recombination (HR) genes, including BRCA1/2, had improved survival versus patients without HR mutations, according to a mutational analysis of the phase III GOG 218 study presented at the 2016 Society of Gynecologic Oncology Annual Meeting. The analysis showed that among patients with BRCA1, BRCA2, and non-BRCA HR mutations, respectively, the reduction in the risk of death, regardless of the treatment received, was 26%, 64%, and 33%, compared with patients without HR mutations.
The risk of disease progression was decreased by 20%, 48%, and 27%, respectively. The findings also demonstrated that HR mutations did not mitigate the benefit of adding bevacizumab to standard care. In the primary GOG 218 analysis, add-on bevacizumab followed by maintenance bevacizumab improved progression-free survival by 3.8 months versus chemotherapy alone in the frontline setting for patients with stage III/IV ovarian cancer.
Novel Therapies on Horizon for NHL
Two presentations at the 20th Annual International Congress on Hematologic Malignancies highlighted novel therapies on the horizon for patients with follicular lymphoma and chronic lymphocytic leukemia. In a talk by John P Leonard, MD, he highlighted that nearly 80% of patients die with, but not of follicular lymphoma. However, for the 20% who die of the disease, novel agents and combinations are still needed.
The combination of rituximab and lenalidomide could be practice changing for follicular lymphoma, as could further use of idelalisib and ibrutinib. Additionally, PD-1 inhibitors, although not effective enough alone, could work well in combination approaches with CD20 inhibitors.
In a talk by Susan O'Brien, MD, she noted that the current PI3K and BTK inhibitors are very effective, and that waves of new agents are in development. Of the numerous agents in development, the most promising appear to be the PI3K inhibitor TGR-1202, which has shown promising efficacy with a superior toxicity profile compared with idelalisib.
Additionally, the BTK inhibitor acalabrutinib has shown promising early signs of activity along with impressive pharmacokinetic data. However, it's still not clear whether these are "me too" drugs or true next-generation agents; only time and further research will tell.
FDA Approves CE-Melphalan for Myeloma
The FDA approved Captisol-enabled melphalan (Evomela) as a high-dose conditioning treatment for use in patients with multiple myeloma prior to autologous stem cell transplantation, as well as for the palliative treatment of patients with myeloma for whom oral therapy is not appropriate. The approval was based on results from a multicenter, open-label phase IIb study in which the overall response rate to CE melphalan was 95% among 61 patients, with all patients having successful myeloablation (median 5 days post-ASCT) and subsequent neutrophil and platelet engraftment (median, 12-13 days post-ASCT) with no mortality at day 100.
The new formulation is meant to provide better stability, which allows for longer administration durations and slower infusion rates. Additionally, the Captisol component eliminates the need for propylene glycol-containing diluent, which can limit dosing due to renal and cardiac toxicities. Spectrum Pharmaceuticals, the company developing the drug, has noted that Evomela will be available at a similar cost as generic melphalan.
CPX-351 Improves OS in Phase III AML Study
Frontline treatment with CPX-351 (Vyxeos) significantly reduced the risk of death by 31% compared with cytarabine and daunorubicin (7+3) for older patients with high-risk, secondary acute myeloid leukemia, according to data from a phase III trial. The study showed a median OS of 9.56 months with CPX-351 versus 5.95 months with 7+3 (HR, 0.69; P = .005). At 12 months, 41.5% of patients enrolled in the CPX-351 arm remained alive versus 27.6% in the 7+3 arm.
At 24 months, 31.1% of patients enrolled in the CPX-351 arm of the study remained alive compared with 12.3% with 7+3. In the short term, 60-day all-cause mortality was 13.7% versus 21.2% in the CPX-351 and control arm, respectively. Induction response rates (complete remission [CR] plus complete remission with incomplete hematologic recovery [CRi]) were 47.7% for CPX-351 versus 33.3% for 7+3, yielding a relative benefit of 43.2% with the investigational treatment (P = .016).
For CR alone, the rates were 37.3% and 25.6%, between CPX-351 and 7+3, respectively (P = .04). Based on results from the phase III study, Celator, the company developing the drug, announced plans to submit a new drug application to the FDA later in 2016. The company expects to present data from the study at the 2016 ASCO Annual Meeting.
Atezolizumab Entering Intriguing Combo Trials
The PD-L1 inhibitor atezolizumab will be explored in phase Ib/II trials with the CAR T-cell therapy KTE-C19 for patients with non-Hodgkin lymphoma and with the CD38 monoclonal antibody daratumumab for patients with multiple myeloma and solid tumors. Atezolizumab is currently being explored with lenalidomide for patients with multiple myeloma. As part of the agreement between Janssen and Roche, this study will be amended to include an arm looking at atezolizumab and daratumumab along with either lenalidomide or pomalidomide.
The CAR T-cell therapy plus atezolizumab study is anticipated to begin this year and will sponsored by Kite Pharma, which is the developer of the KTE-C19. The study will look specifically at the combination in patients with refractory, aggressive NHL. The two agents are expected to display synergistic activity.