Early ASCO Findings Highlight Week in Cancer News
Recent advances and updates in oncology and cancer drug development.
FDA Approves Atezolizumab in Bladder Cancer
The FDA granted the PD-L1 inhibitor atezolizumab an accelerated approval as a treatment for patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or after platinum-based chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery. The approval was based on data from the phase II IMvigor 210 study, in which atezolizumab had an overall response rate of 14.8% in patients with locally advanced or mUC, regardless of PD-L1 expression.
Among patients with PD-L1 expression ≥5%, ORR was 26%. Complete response rates in the overall and high—PD-L1 expression groups were 5.5% and 12%, respectively. The PD-L1 assay Ventana PD-L1 (SP142) was concurrently approved as a companion diagnostic.
Nivolumab Approved for Hodgkin Lymphoma
The FDA granted nivolumab accelerated approval for the treatment of patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin. The approval was based on an objective response rate of 65% in 95 patients enrolled in 2 single-arm trials of nivolumab in patients with relapsed or refractory cHL.
Nivolumab is now the first PD-1 inhibitor approved for a hematologic malignancy. The complete remission rate with the PD-1 inhibitor was 7% and the median duration of response was 8.7 months. The accelerated approval of nivolumab in cHL is contingent on the confirmatory outcomes of a phase III trial.
Upfront Cabozantinib Bests Sunitinib in Phase II CABOSUN Trial
Cabozantinib significantly improved progression-free survival compared with sunitinib in treatment-naive patients with advanced renal cell carcinoma in the phase II CABOSUN trial. The safety profile for cabozantinib was similar to previously reported outcomes with the treatment in advanced RCC. The primary outcome measure was PFS, with secondary endpoints including overall survival and objective response rate.
Dr Toni K. Choueiri called the results extremely exciting, since they represent the first time that a therapy has shown superiority to sunitinib in the frontline setting. Cabozantinib was recently approved in April 2016 as a treatment for patients with advanced RCC who have received prior antiangiogenic therapy. Exelixis plans to submit the full CABOSUN results for presentation at an upcoming medical meeting and communicate with regulatory authorities about a potential first-line cabozantinib indication in RCC.
CPX-351 Granted Breakthrough Designation for AML
The FDA granted a breakthrough therapy designation to CPX-351 as a treatment for patients with therapy-related acute myeloid leukemia or AML with myelodysplasia-related changes. The designation was primarily based on a phase III trial in which CPX-351 significantly reduced the risk of death by 31% compared with cytarabine and daunorubicin (7+3) for older patients with high-risk, secondary AML. The study showed a median overall survival of 9.56 months with CPX-351 versus 5.95 months with 7+3 (HR, 0.69; P = .005). 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.
Complete response rates were 37.3% and 25.6%, between CPX-351 and 7+3, respectively (P = .04). A statistically significant difference was not observed for grade 3/4 adverse events between the 2 arms. Full and updated findings from the phase III study will be presented at the ASCO Annual Meeting.
Ribociclib/Letrozole Improves PFS in Breast Cancer
The combination of the CDK4/6 inhibitor ribociclib and letrozole significantly improved progression-free survival compared with letrozole alone for patients with HR-positive, HER2-negative advanced breast cancer, according to findings from the phase III MONALEESA-2 study. The improvement in PFS was identified at an interim analysis by an independent data monitoring committee, which recommended the study should be stopped, according to the developer of ribociclib, Novartis.
Data from the study have not yet been released and are being prepared for presentation at an upcoming medical meeting. A number of clinical trials continue to assess ribociclib as a treatment for patients with breast cancer.
Two Positive Phase III Studies and European Approval for Daratumumab
The European Commission has granted conditional marketing approval to daratumumab for the treatment of patients with relapsed/refractory multiple myeloma previously treated with a proteasome inhibitor and an immunomodulatory agent who progressed on their last therapy. The approval—which was based on data from the phase II SIRIUS MMY2002 study, the phase I/II GEN501 study, and 3 other supportive studies—is contingent on results from confirmatory trials.
A combined analysis from the MMY2002 and GEN501 trials found that at a mean follow-up of 14.8 months, the estimated median overall survival was 20 months (95% CI, 15 months — not yet estimable) with daratumumab (16 mg/kg) monotherapy in heavily pretreated patients with myeloma.
The FDA granted daratumumab an accelerated approval in November 2015 as a monotherapy for patients with multiple myeloma following at least 3 prior therapies. Findings from the phase III CASTOR study for daratumumab will be presented at the ASCO Annual Meeting. In the trial, adding daratumumab to bortezomib and dexamethasone reduced the risk of progression by 61% (HR, 0.39; P <.0001).
Additionally, the phase III POLLUX trial also showed promising results. In this trial, daratumumab was combined with lenalidomide and dexamethasone and showed a reduction in the risk of disease progression of 63% in patients with relapsed/refractory multiple myeloma.
Early ASCO Findings Presented
The ASCO Abstracts were recently released, accompanied by a press briefing highlighting results from a handful of studies. In this release, 3-year findings were announced from the phase I KEYNOTE-001 study, which showed 40% of patients were alive at 3 years when treated with pembrolizumab. The median overall survival was 24.2 years.
Another study found that OS was linked with tumor location for patients with colorectal cancer. The median OS was nearly 14 months longer in patients with left-sided tumors versus right.
A large analysis of several studies found that outcomes were significantly better in clinical trials that utilized a biomarker-based treatment selection strategy compared with non-personalized approaches. In the analysis, there was a response rate of 31% in the biomarker driven arm compared with just 5% in the non-personalized group (P <.0001).
Phase III Olaparib Trial Misses OS Endpoint in Gastric Cancer
The combination of olaparib and paclitaxel failed to improve overall survival compared with paclitaxel and placebo in the phase III GOLD trial for patients with advanced gastric cancer. The study included 525 patients from China, Japan, South Korea, and Taiwan with gastric and gastroesophageal junction tumors who progressed following frontline therapy.
The primary endpoint of the study was OS, with secondary endpoints focused on progression-free survival, safety, and response. Tumors samples from resected tissue or a biopsy were tested for ATM expression, with 18% of the participants testing negative. According to AstraZeneca, outcomes were similar between the ATM-negative group and the entire population. Additionally, adverse events with the combination were similar to those seen with single-agent paclitaxel.