Flood of Drug Approvals Highlight Week in Cancer News

FDA Approves Pembrolizumab for Frontline PD-L1+ NSCLC

Exactly 2 months ahead of a Christmas Eve PDUFA date, the FDA has approved pembrolizumab for the frontline treatment of patients with metastatic non—small cell lung cancer whose tumors have ≥50% PD-L1 expression based on an FDA-approved test and who do not harbor EGFR or ALK aberrations.

The approval is based on data from the phase III KEYNOTE-024 trial, in which single-agent pembrolizumab reduced the risk of death by 40% and improved median progression-free survival by 4.3 months compared with doublet chemotherapy for untreated patients with advanced NSCLC with PD-L1 expression on ≥50% of cells. Along with the frontline approval, the FDA also authorized an update to pembrolizumab’s label to include data from the KEYNOTE-010 trial, which examined the PD-1 inhibitor in the second-line setting and beyond for patients with NSCLC and PD-L1 expression levels of ≥1% who have progressed on platinum-based chemotherapy and EGFR- or ALK-targeted therapy for individuals harboring those aberrations. The action converts the accelerated approval pembrolizumab previously received in this setting to a full approval.

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FDA Approves Atezolizumab for Lung Cancer

The FDA has approved atezolizumab for the treatment of patients with metastatic non—small cell lung cancer who have progressed after a platinum-containing regimen and an FDA-approved targeted therapy for those patients harboring EGFR or ALK abnormalities. The approval is based on multiple clinical trials, the largest being the phase III OAK trial, which was presented at the 2016 ESMO Congress.1 In the study, atezolizumab reduced the risk of death by 26% compared with docetaxel in patients with advanced NSCLC following the failure of platinum-based chemotherapy.

The median overall survival was improved by 4.2 months with the PD-L1 inhibitor versus chemotherapy. In the intent to treat population (N = 850), the median OS was 13.8 months in the atezolizumab arm (n = 425) versus 9.6 months in the docetaxel arm (n = 425; HR, 0.74; 95% CI, 0.63-0.87; P = .0004). The PFS was 2.8 months versus 4 months (HR, 0.95), respectively. The ORR and DoR were 13.6% versus 13.4%, and 16.3 versus 6.2 months, respectively. The survival benefit with atezolizumab was observed regardless of PD-L1 status or histology.

See more http://www.onclive.com/web-exclusives/fda-approves-atezolizumab-for-lung-cancer

FDA Approves Olaratumab for Soft Tissue Sarcoma

The FDA has granted an accelerated approval to the PDGFRα antagonist olaratumab in combination with doxorubicin for the treatment of patients with advanced soft tissue sarcoma who are not candidates for radiotherapy or surgery, based on an improvement in overall survival in the phase II JGDG study. In the pivotal trial, the combination of olaratumab with doxorubicin reduced the risk of death by 48% compared with doxorubicin alone for patients with advanced STS (HR, 0.52; 95% CI, 0.34-0.79, P <.05). Median OS in the intent-to-treat population (n = 129) was improved by 11.8 months with the olaratumab combination versus doxorubicin alone.

The median OS was 26.5 months with the combination versus 14.7 months with doxorubicin alone. By blinded independent review, 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). By investigator assessment, median PFS was 6.6 months with olaratumab plus doxorubicin compared with 4.1 months with doxorubicin alone (HR, 0.67; 95% CI, 0.44-1.02). By independent assessment, the objective response rate was 18.2% in the combination arm versus 7.5% in the doxorubicin arm.

See more http://www.onclive.com/web-exclusives/fda-approves-olaratumab-for-soft-tissue-sarcoma

FDA Grants Nivolumab Priority Review for Urothelial Carcinoma

The FDA has granted a priority review designation to nivolumab as a treatment for patients with locally advanced unresectable or metastatic urothelial carcinoma following progression on a platinum-containing therapy, based on findings from the phase II CheckMate-275 study. The agency is scheduled to make a decision on the application for the PD-1 inhibitor by March 2, 2017, as part of the Prescription Drug User Fee Act.

In the study, which was presented at the 2016 ESMO Annual Meeting, the objective response rate was 19.6% for nivolumab in patients with platinum-refractory metastatic urothelial carcinoma. Across the 270-patient study, the median progression-free survival was 2.0 months and the median overall survival was 8.74 months. After a median follow-up of 7 months, 24.4% of patients remained on therapy. The median duration of response was not yet reached, with 76.9% of responses ongoing at the time of the analysis. The median time to response was 1.9 months. Responses consisted of a complete response rate of 2.3% and a partial response rate of 17.4%. The stable disease rate was 22.6%.

See more http://www.onclive.com/web-exclusives/fda-grants-nivolumab-priority-review-for-urothelial-carcinoma

Pembrolizumab Improves Survival in Pretreated Bladder Cancer

Pembrolizumab improved survival compared with chemotherapy in previously treated patients with advanced urothelial cancer in the phase III KEYNOTE-045 trial. After meeting the overall survival endpoint, the trial was halted based on the recommendation of an independent data monitoring panel. The study data are not yet available; however, Merck reported that the safety profile for pembrolizumab was consistent with previous trials involving patients with advanced urothelial cancer.

Early results from a preplanned interim analysis from the KEYNOTE-052 phase II trial of first-line pembrolizumab in cisplatin-ineligible patients with metastatic urothelial cancer were recently presented at the 2016 ESMO Congress. In this trial, the ORR at a median follow-up of 8 months was 24% (95% CI, 16.0-33.6). Pembrolizumab treatment yielded a rapid response with a median time to response of 2 months (range, 0.1-13.4).

See more http://www.onclive.com/web-exclusives/pembrolizumab-improves-survival-in-pretreated-bladder-cancer

Denosumab Delays SREs in Multiple Myeloma

Denosumab is noninferior to the standard of care zoledronic acid at delaying skeletal-related events for patients with multiple myeloma, according to topline findings from the phase III 482 study. In the study, the hazard ratio for the primary endpoint of time to first SRE was 0.98 (95% CI, 0.85-1.14), which fell within the parameters of noninferiority. The hazard ratio for overall survival between denosumab and zoledronic acid was 0.90 (95% CI, 0.70-1.16).

Secondary endpoints of the study focused on superiority for the RANK ligand inhibitor versus the bisphosphonate for time to first SRE and time to first and subsequent SRE, which were defined as fracture, radiation to bone, surgery to bone, or spinal cord compression. In the initial analysis, these secondary endpoints were not met. The adverse events in the study were consistent with the known safety profile for denosumab. The most common AEs in the denosumab arm were diarrhea and nausea, both of which occurred in greater than 25% of patients. Findings from the study will be presented at an upcoming medical meeting and will be submitted to the FDA.

See more http://www.onclive.com/web-exclusives/denosumab-effectively-delays-sres-in-multiple-myeloma

FDA Updates Enzalutamide Label in mCRPC

The FDA has updated the label for enzalutamide in metastatic castration-resistant prostate cancer to include new data from the phase II TERRAIN study. The trial randomized 375 chemotherapy-naïve patients with mCRPC in a 1:1 ratio to receive enzalutamide at 160 mg orally once daily or bicalutamide at 50 mg once daily.

Overall, enzalutamide reduced the risk of radiographic progression or death by 40% compared with bicalutamide. The median radiographic progression-free survival was improved by 6.1 months with enzalutamide. The median radiographic progression-free survival was 19.5 months with enzalutamide compared with 13.4 months with bicalutamide (HR, 0.60; 95% CI, 0.43-0.83).

See more http://www.onclive.com/web-exclusives/fda-updates-enzalutamide-label-in-mcrpc

EC Approves Liposomal Irinotecan for Pancreatic Cancer

The European Commission has approved pegylated liposomal irinotecan in combination with fluorouracil and leucovorin for patients with metastatic pancreatic adenocarcinoma following progression on a gemcitabine-based therapy. The approval was based on findings from the phase III NAPOLI-1 trial, which demonstrated a 1.9-month improvement in overall survival with the addition of liposomal irinotecan to 5-FU and leucovorin.

In the combination arm, the median OS was 6.1 months compared with 4.2 months with 5-FU and leucovorin alone (HR, 0.67; 95% CI, 0.49-0.92; P = .012). The EC’s approval decision followed a positive recommendation from the Committee for Medicinal Products for Human Use. Pegylated liposomal irinotecan is now approved for use in this setting in the 28 countries of the European Union, as well as in Iceland, Liechtenstein and Norway.

See more http://www.onclive.com/web-exclusives/ec-approves-liposomal-irinotecan-for-pancreatic-cancer