Top news of the week in oncology and cancer drug development.
FDA Grants Inotuzumab Ozogamicin Priority Review for ALL
The FDA has granted a priority review designation to the anti-CD22 antibody-drug conjugate inotuzumab ozogamicin for the treatment of patients with relapsed or refractory acute lymphoblastic leukemia (ALL), based on findings from the phase III INO-VATE trial. Under the priority review program, the FDA will decide on the biologics license application for inotuzumab ozogamicin within 6 months compared with the standard 10-month review.
The accelerated review timeline follows a breakthrough therapy designation for ALL received by inotuzumab ozogamicin in October 2015. Under the Prescription Drug User Fee Act, the FDA will make its decision on the application in August 2017. In the open-label phase III trial that was instrumental in the priority review, the risk of progression or death was reduced by 55% with inotuzumab ozogamicin versus standard therapy (HR, 0.45; 97.5% CI, 0.43-0.61; P <.001). Overall survival was improved with inotuzumab ozogamicin versus chemotherapy; however, this improvement was not statistically significant (HR, 0.77; 97.5% CI, 0.58-1.03; P = .04).
Olaparib Improves PFS in Phase III BRCA+ Breast Cancer Trial
Olaparib (Lynparza) improved progression-free survival versus standard chemotherapy in patients with BRCA-positive, HER2-negative breast cancer, according to findings from the phase III OLYMPIAD trial announced by AstraZeneca, the manufacturer of the PARP inhibitor. The company is continuing to evaluate the study data and plans to present the full results at an upcoming medical meeting, as well as communicate with regulatory authorities regarding the data.
The initial safety data are consistent with previous olaparib studies, according to AstraZeneca. Positive results for olaparib in this setting were previously shown in a phase II proof-of-concept trial (NCT00494234) published in the The Lancet in 2010. The study assigned patients to olaparib at 400 mg twice daily or 100 mg twice daily. Among patients in the 400-mg cohort, the overall response rate (ORR) was 41% (11/27; 95% CI, 25-59), and the ORR was 22% (6/27; 95% CI, 11-41) for the 100-mg cohort.
Combination Makes First-Line Case for Metastatic PD-L1+ RCC
Patients with PD-L1—positive metastatic renal cell carcinoma had a 36% reduction in the risk of progression or death when treated in the first-line setting with the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) instead of sunitinib (Sutent), according to results of a randomized phase II trial presented at the 2017 Genitourinary Cancers Symposium. The median progression-free survival (PFS) was almost twice as long with the combination therapy, at 14.7 months versus 7.8 months.
Although the combination failed to improve PFS in the overall population (primary endpoint), the phase II results made a compelling case for a randomized phase III evaluation of the atezolizumab-bevacizumab combination, which has already begun. The overall response rate differed little among the three groups in the ITT analysis: 32% with the combination, 29% with sunitinib, and 25% with atezolizumab monotherapy. An analysis of patients with ≥1% PD-L1 expression showed response rates of 46% with the combination, 28% with atezolizumab alone, and 27% with sunitinib.
Durvalumab Impresses in Advanced Urothelial Cancer
The PD-L1 inhibitor durvalumab demonstrated compelling clinical activity and a manageable safety profile as second-line therapy for locally advanced or metastatic urothelial cancer, according to updated data from a phase I/II study presented at the 2017 Genitourinary Cancers Symposium. Following treatment with durvalumab, one-fourth of 103 patients (24%) remained alive without progression at 6 months as did 17% at 12 months.
The overall survival rate was 60% at 6 months and 51% at 12 months. Durvalumab led to an overall response rate of 20.4%, and patients with and without PD-L1 expression had objective responses. Twenty-one patients (20.4%) attained objective responses with durvalumab, including 4 complete responses. Responses occurred after a 1.4-month median duration of treatment, and 17 of the responses persisted for at least 6 months. The median duration of response had yet to be reached.
Olaparib, Durvalumab Combo Active in Prostate Cancer
Half of a small group of patients with metastatic castration-resistant prostate cancer had a PSA response during treatment with the PD-L1 inhibitor durvalumab and the PARP inhibitor olaparib (Lynparza), according to preliminary results from an ongoing trial. Overall, 8 out of 10 patients had a reduction in PSA level, including 5 patients who had declines in PSA tests exceeding 50% or more from baseline. The cohort had a median progression-free survival of 7.8 months.
Among 7 patients followed for more than 2 months, grade 3/4 adverse events consisted of 2 cases of anemia and 1 each of thrombocytopenia, lymphopenia, neutropenia, nausea, fatigue, urinary tract infection, and lung infection, as reported at the 2017 Genitourinary Cancers Symposium.The best PSA responses ranged from a decline of 15% to a decline of 99%. Other patients had declines from baseline of 94%, 79%, 73%, and 59%. Responses were observed in patients who had only bone metastases, and in those who had bone plus soft-tissue/visceral metastases, regardless of the number of prior lines of therapy, and in patients with or without mutations in DNA repair pathways.
Ipilimumab Broadens Nivolumab Activity in Urothelial Cancer
Five of 8 evaluable patients with metastatic urothelial cancer benefited from the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) after having no response to single-agent nivolumab, according to study findings reported at the 2017 Genitourinary Cancers Symposium. By radiographic assessment there was 1 partial response and 4 patients with stable disease. By RECIST criteria, 4 of the 8 evaluable patients benefited from the ipilimumab/nivolumab combination, consisting of 1 partial response and 3 patients with stable disease. The combination was associated with a modest increase in toxicity, but was generally well tolerated.
Tivantinib Falls Short in Phase III Liver Cancer Trial
Tivantinib did not improve overall survival (OS) compared with placebo as a second-line therapy for patients with MET-overexpressing inoperable hepatocellular carcinoma in the phase III METIV-HCC study, according to a statement from Daiichi Sankyo and ArQule, the companies codeveloping the MET inhibitor. While the companies did not release findings from the study, they did note that OS, progression-free survival, and safety data would be presented at an upcoming medical meeting.