Recent advances and updates in oncology and cancer drug development.
Inotuzumab Ozogamicin Effective in ALL
The anti—CD22 antibody-drug conjugate inotuzumab ozogamicin demonstrated significantly improved progression-free survival and complete remission rates compared with chemotherapy for patients with relapsed or refractory acute lymphoblastic leukemia. Pfizer is discussing data from the study with the FDA. In the phase III trial, inotuzumab ozogamicin demonstrated a median PFS of 5.0 months compared with 1.8 months with standard chemotherapy (HR, 0.45; P <.001).
The CR or CR with incomplete hematologic recovery rate was 80.7% with inotuzumab ozogamicin compared with 29.4% of those who received standard chemotherapy. The 2-year overall survival (OS) rate for inotuzumab ozogamicin was 23% compared with 10% for chemotherapy. There was a 23% advantage seen in the median OS with inotuzumab ozogamicin versus chemotherapy; however this did not pass the bar for statistical significance (HR, 0.77; P = .04).
Daratumumab Triplet Highly Effective in Myeloma
Combining the CD38-targeted antibody daratumumab with lenalidomide and dexamethasone reduced the risk of disease progression by 63% versus lenalidomide and dexamethasone alone in patients with relapsed/refractory multiple myeloma, according to findings from the phase III POLLUX (MMY3003) trial. At a median follow-up of 13.5 months, the median progression-free survival was not yet reached in the daratumumab arm versus 18.4 months with lenalidomide/dexamethasone alone (HR, 0.37; P <.0001).
The ORR was 93% versus 76%, respectively, (P <.0001). The VGPR or better rate was 76% with daratumumab versus 44% in the control arm (P <.0001) and the compete response rates were 43% and 19%, respectively (P <.0001). This is the second phase III trial to demonstrate a PFS benefit with a daratumumab triplet in relapsed/refractory multiple myeloma, with the first being the CASTOR study, which was presented at ASCO. Data from the 2 studies are being discussed with the FDA for an expanded indication.
Antibody-Drug Conjugate Combo Improves CRs in AML
Frontline treatment with the CD33-directed antibody-drug conjugate vadastuximab talirine plus a hypomethylating agent induced deep and durable remissions for older patients with acute myeloid leukemia, according to findings from a phase I study. In the trial, the combination of vadastuximab talirine and an HMA showed an objective response rate of 76%, which included a complete remission rate of 41%. An additional 30% of patients experienced a CR with incomplete platelet or neutrophil recovery making the overall CR/CRi rate of 71%.
There were no dose-limiting toxicities reported. Although still premature, the estimated overall survival from the first 25 patients enrolled in the study was 12.75 months with the combination. The median relapse-free survival was 7.7 months, with 51% remaining alive at the data cutoff. Based on the promise of these findings, Seattle Genetics, the company developing the antibody-drug conjugate, launched a pivotal phase III study for older patients with newly diagnosed AML. If positive, results of this study could support a regulatory filing.
Blinatumomab Doubles Median OS in ALL in Phase III Study
The median overall survival with the anti-CD19 immunotherapy blinatumomab was 7.7 months versus 4 months with standard chemotherapy in patients with Philadelphia chromosome—negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia, according to results from the phase III TOWER study. Treatment with blinatumomab reduced the risk of death by 29% versus standard chemotherapy (HR, 0.71; 95% CI, 0.55-0.93; P = .012). The CR rate with blinatumomab was 39% versus 19% with standard chemotherapy (P <.001).
The combined CR/CRh/CRi rates were 46% versus 28%, respectively (P = .001). The OS benefit with blinatumomab was observed across prespecified patient subgroups based on age, prior salvage therapy, or alloSCT. The study was halted early for efficacy based on the recommendation of an an independent data monitoring committee. The TOWER study is the confirmatory study for the accelerated approval of blinatumomab, which the FDA granted in December 2014 based on phase II data demonstrating strong clinical activity with the agent in ALL.
TKI Stop Possible in Select CML Patients
Tyrosine kinase inhibitors can safely be halted in select patients with chronic phase chronic myeloid leukemia followed a maintained deep molecular remission, according to findings from the large EURO-SKI trial. After a median follow-up of 10 months, 62% of patients were still in major molecular remission 6 months after TKI-stop, 56% were still in remission after 12 months, and 51% were still in remission after 24 months.
Most patients in the trial were previously receiving the TKI imatinib. Based on this, as well as previous trial data, researchers have determined an ideal time frame for physicians to consider the stopping TKI for patients with chronic phase CML. The molecular relapse-free survival was 62% at 6 months (95% CI, 58-65), 56% at 12 months (95% CI, 52- 59), and 51% at 24 months (95% CI, 47- 55).
Bevacizumab/Erlotinib Combo Approved for NSCLC in Europe
On Wednesday last week, the European Commission approved bevacizumab in combination with erlotinib as a frontline treatment for patients with unresectable advanced, metastatic, or recurrent EGFR-mutant non—small cell lung cancer.
The approval was based on findings from the phase II JO25567 study, which showed a 46% reduction in the risk of progression or death with the combination versus single-agent erlotinib. The median progression-free survival with the addition of bevacizumab was 16 versus 9.7 months with erlotinib alone (HR, 0.54; P = .0015). Overall survival data were immature at the time of the analysis.
The objective response rate in the combination arm was 69% versus 64% with erlotinib alone (P = .4951). Grade 3/4 adverse events (AEs) were experienced by 91% of patients treated with the combination compared with 53% with the single-agent. AEs led to erlotinib discontinuation for 16% of patients in the combination arm versus 18% for the single-agent group. In response to the news, Jack West, MD, noted on Twitter that the combination of bevacizumab and erlotinib was his preferred method. He hopes for further data and an eventual FDA approval.