Top news of the week in oncology and cancer drug development.
NY Lung, CFS Review Latest Advances
The 2016 CFS did not fail to impress, with many updates on the latest treatment strategies across a variety of cancer types. The symposium focused on the latest advances in immunotherapy and future directions for this treatment approach.
See more coverage from the event http://www.onclive.com/conference-coverage/cfs-2016
The NY Lung meeting explored the ever-evolving world of lung cancer treatment. The meeting hit on both targeted therapies and immunotherapies. Presenters touched on novel EGFR and ALK inhibitors in the morning sessions and new strategies for immunotherapies in the evening.
See more coverage from the event http://www.onclive.com/conference-coverage/ny-lung-2016
FDA Approves Nivolumab for Head and Neck Cancer
The FDA has approved nivolumab for patients with metastatic or recurrent squamous cell carcinoma of the head and neck following progression on platinum-based therapy. The approval was based on the CheckMate-141 study, in which the median overall survival with nivolumab was 7.5 months compared with 5.1 months with investigator's choice (HR, 0.70; 95% CI, 0.52-0.92; P = .0101).
The objective response rate was 13.3% with nivolumab and 5.8% for investigator's choice. The ORR in the nivolumab arm consisted of 6 complete responses (2.5%) and the stable disease rate was 22.9%. In the investigator's choice arm, 1 patient had a complete response and the SD rate was 35.5%. The median progression-free survival was 2 months with nivolumab versus 2.3 months with investigator's choice (HR, 0.89; 95% CI, 0.70-1.10; P = .3236).
The 6-year PFS rates were 19.7% for nivolumab and 9.9% for investigator's choice of therapy. The 1-year OS rates were 36% with nivolumab (95% CI, 28.5-43.4) compared with 16.6% for investigator’s choice (95% CI, 8.6-26.8). Similar improvements in survival were seen across demographic subgroups.
See more http://www.onclive.com/web-exclusives/fda-approves-nivolumab-for-head-and-neck-cancer
FDA Grants Midostaurin Priority Review for AML
The FDA granted a priority review to a new drug application for midostaurin (PKC412) for adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia or advanced systemic mastocytosis. The NDA is based on the phase III RATIFY trial in AML and a single-arm phase II study of patients with SM. In the RATIFY trial, the addition of midostaurin to standard chemotherapy reduced the risk of death by 23% compared with chemotherapy alone in patients with AML who harbored an FLT3 mutation.
After censoring for patients who received stem cell transplants, the overall survival benefit with midostaurin remained steady at 25%. The phase II data submitted for midostaurin in SM showed that the drug had an overall response rate of 60% and a median duration of response of 24.1 months. The median OS was 28.7 months. The priority review follows an FDA breakthrough therapy designation granted to midostaurin in February 2016 for newly diagnosed patients with FLT3-mutated AML. Under the expedited designation, the NDA will be reviewed within 6 months, compared with the standard 10-month review.
See more http://www.onclive.com/web-exclusives/fda-grants-midostaurin-priority-review-for-aml
Second-Line Nivo/Ipi Effective in Urothelial Carcinoma
The combination of nivolumab and ipilimumab led to a high response rate and improved overall survival versus historical controls for patients with pretreated metastatic urothelial carcinoma, according to findings from the phase I/II CheckMate-032 study. In the open-label study, the objective response rate for patients receiving nivolumab at 1 mg/kg with ipilimumab at 3 mg/kg (N1/I3; n = 26) was 38.5% (95% CI, 20.2-59.4), with a complete response rate of 3.8%.
In patients receiving nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg (N3/I1; n = 104), the ORR was 26% (95% CI, 17.9-35.5) and the CR rate was 2.9%. The median progression-free survival in the N1/I3 group was 4.3 months (95% CI, 1.6-8.2) and the median OS was 10.2 months (95% CI, 4.5-NR). The median PFS in the N3/I1 arm was 2.6 months (95% CI, 1.4-3.9) and the median OS was 7.3 months (5.6-11.4).
See more http://www.onclive.com/web-exclusives/nivolumab-ipilimumab-combo-highly-effective-for-pretreated-metastatic-urothelial-carcinoma
Nivolumab Extends Survival in Gastric Cancer
Treatment with nivolumab significantly extended overall survival compared with placebo for patients with unresectable, advanced, or recurrent gastric cancer who were refractory or intolerant to standard therapy, according to findings from the phase III ONO-4538-12 trial. The phase III doubled-blind trial was conducted by Ono Pharmaceuticals, which is the company developing nivolumab in Japan, Korea, and Taiwan.
The primary endpoint of the study was OS, and secondary endpoints focused on progression-free survival and objective response rate. Findings from the study were not yet announced, and will be prepared for presentation at an upcoming meeting, according to BMS. In a previous phase I/II study, the median OS was 5.03 months with nivolumab (95% CI, 3.35-12.42). The 12-month OS rate was 36%. The median PFS was 1.36 months (95% CI, 1.25-1.51) and the 12-month PFS rate was 7%.
See more http://www.onclive.com/web-exclusives/nivolumab-improves-os-in-phase-iii-gastric-cancer-study
Pembrolizumab Extends OS Versus Chemo for Bladder Cancer
Treatment with pembrolizumab improved overall survival by 2.9 months compared with chemotherapy for patients with advanced urothelial carcinoma whose disease progressed after prior treatment, according to findings from the phase III KEYNOTE-045 trial. In the KEYNOTE-045 trial, patients treated with pembrolizumab achieved a median OS of 10.3 months (95% CI, 8.0-11.8) compared with 7.4 months (95% CI, 6.1-8.3) for those who received a chemotherapy regimen.
The difference resulted in a hazard ratio of 0.73 (95% CI, 0.59-0.91). The survival benefit was observed regardless of PD-L1 expression status and there were fewer adverse events with the immunotherapy. Pembrolizumab therapy also resulted in a significantly higher objective response rate of 21.1% compared with 11.4% with chemotherapy (P = .0011). Similarly, the complete response rate was much higher with pembrolizumab at 7.0% compared with a 3.3% CR with chemotherapy.
See more http://www.onclive.com/conference-coverage/sitc-2016/pembrolizumab-os-benefit-sets-new-benchmark-in-secondline-bladder-cancer
Lirilumab/Nivolumab Combo Promising for Head and Neck Cancer
The combination of the KIRs inhibitor lirilumab with the PD-1 inhibitor nivolumab resulted in an objective response rate of 24.1% in patients with squamous cell carcinoma of the head and neck. In the phase I/II study, 29 patients with SCCHN were evaluable for response, of which 3 had a complete response (10.3%) and 4 had a partial response (13.8%), 2 of which were near complete responses with a ≥80% reduction in tumor size.
The 6-month overall survival rate with lirilumab plus nivolumab was 90% and the 12-month OS rate was 60%. None of the 9 patients with PD-L1-negative disease responded to therapy. In those with PD-L1 expression on ≥1% of cells (n = 17), the response rate was 41.2%. When looking at PD-L1 expression on ≥5% of cells (n = 11), the ORR was 54.5%, which was similar to the ≥50% expression cutoff (n = 7; ORR, 57.1%).
See more http://www.onclive.com/conference-coverage/sitc-2016/lirilumabnivolumab-combo-highly-effective-in-head-and-neck-cancer
FDA Grants Brentuximab Vedotin Breakthrough Designation in CTCL
Brentuximab vedotin has received an FDA breakthrough therapy designation for the treatment of patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large cell lymphoma following at least 1 prior systemic therapy, according to Seattle Genetics, the manufacturer of the anti-CD30 antibody-drug conjugate. The designation, which will expedite the development and review of brentuximab vedotin for use in these 2 most common subtypes of cutaneous T-cell lymphoma, is based on data from the phase III ALCANZA trial.
At a median follow-up of 17.5 months, the median PFS was 16.7 months with brentuximab vedotin versus 3.5 months with physician’s choice (HR, 0.270; 95% CI, 0.169-0.430; P <.0001). The ORR was 67% (n = 43) versus 20% (n = 13; P <.0001), with CR rates of 16% versus 2% (P = .0046), in the brentuximab vedotin and control arms, respectively. Symptom reduction, as measured by Skindex-29, was significantly better with brentuximab vedotin versus physician’s choice (-27.96 vs -8.62; P <.0001).
See more http://www.onclive.com/web-exclusives/fda-grants-brentuximab-vedotin-breakthrough-designation-in-ctcl
Frontline Olaratumab for Sarcoma in Europe
The European Commission has granted an accelerated approval to olaratumab in combination with doxorubicin as a frontline therapy for patients with advanced soft tissue sarcoma, making it the first new therapy for this indication in over 40 years. The decision, which was preceded by a positive opinion from the Committee for Medicinal Products for Human Use, was based on findings from the phase II JGDG study, which showed an 11.8-month improvement in overall survival with the PDGFRα antagonist versus doxorubicin alone.
The median OS was 26.5 months with the combination versus 14.7 months with doxorubicin alone (HR, 0.463; 95% CI, 0.301-0.710, P = .0003). median progression-free survival was 8.2 versus 4.4 months for the olaratumab combo and doxorubicin alone, respectively (HR, 0.67; 95% CI, 040-1.12; P = .1208). the objective response rate was 18.2% in the combination arm versus 7.5% in the doxorubicin arm. The complete response rate to the olaratumab combination was 4.5% and the partial response rate was 13.6%. The CR rate was 1.5% in the doxorubicin arm.
See more http://www.onclive.com/web-exclusives/ec-approves-frontline-olaratumab-for-soft-tissue-sarcoma