Top news of the week in oncology and cancer drug development.
FDA Approves Frontline Pembrolizumab Combo for NSCLC
The FDA has granted an accelerated approval to pembrolizumab (Keytruda) for use in combination with pemetrexed plus carboplatin as a frontline treatment for patients with metastatic or advanced nonsquamous non—small cell lung cancer, regardless of PD-L1 expression. The approval was based on part 2 of cohort G in the KEYNOTE-021 trial, in which the pembrolizumab triplet elicited an objective response rate of 55% compared with 29% with the chemotherapy agents alone (P = .0032).
The median progression-free survival (PFS) was 13.0 months with the addition of pembrolizumab versus 8.9 months for chemotherapy alone (HR, 0.53; 95% CI, 0.31-0.91; P = .0205). The 6-month PFS rate was 77% with pembrolizumab (95% CI, 64-86) compared with 63% for chemotherapy alone (95% CI, 49-74).
FDA Approves Avelumab for Bladder Cancer
The FDA has granted an accelerated approval to the PD-L1 inhibitor avelumab (Bavencio) for the treatment of patients with locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. The approval was based on data from the urothelial carcinoma cohorts of the single-arm, open-label JAVELIN Solid Tumor trial, in which the overall response rate was 13.3% (95% CI, 9.1-18.4) among 226 patients who had been followed for at least 13 weeks, and was 16.1% (95% CI, 10.8-22.8) among 161 patients who had been followed for at least 6 months.
In the ≥6-month follow-up cohort, the 26 responses included 9 (5.6%) complete responses (CRs) and 17 (10.6%) partial response (PRs). In the ≥13 weeks follow-up group, the 30 responses included 9 CRs (4%) and 21 PRs (9.3%).
FDA Approves Co-Packaging of Ribociclib With Letrozole for Metastatic Breast Cancer
The FDA has approved co-packaging of the oral medications ribociclib (Kisqali) and letrozole (Femara) for the treatment of postmenopausal women with HR-positive, HER2-negative advanced breast cancer. With the new Kisqali Femara Co-Pack, patients can obtain a full 28-day cycle of the 2 medicines in 1 package with 1 prescription and 1 copay, and the cost will be the same as that for Kisqali alone, according to Novartis, which manufactures both medications.
The company noted that ribociclib, which helps to slow cancer progression by inhibiting the cyclin-dependent kinase 4 and 6 (CDK 4/6) proteins, can continue to be prescribed separately, along with another aromatase inhibitor (AI). Ribociclib was approved by the FDA on March 13 for use in combination with an AI for this population of women, based on findings from the phase III MONALEESA-2 trial. In that study, the combination of ribociclib and letrozole reduced the risk of progression or death by 44% compared with letrozole plus placebo in the first-line setting for HR+/HER2- advanced breast cancer (HR, 0.556; 95% CI, 0.43-0.72; P <.0001).
Durvalumab Improves PFS in Phase III NSCLC Trial
Durvalumab (Imfinzi) significantly improved progression-free survival (PFS) when used as a sequential treatment in patients with locally-advanced, unresectable non—small cell lung cancer (NSCLC) who had not progressed following standard care with platinum-based chemotherapy and radiotherapy, meeting the primary endpoint of the phase III PACIFIC trial. AstraZeneca, the manufacturer of the PD-L1 inhibitor, intends to present these initial findings from the PACIFIC trial at an upcoming medical meeting.
The company has also initiated talks with regulatory authorities regarding approval for durvalumab for use in this setting. The double-blind PACIFIC trial took place at 235 centers in 26 countries and included an “all-comer” patient population who had locally-advanced, unresectable (stage III) NSCLC with no disease progression after concurrent therapy with platinum-based chemotherapy and radiation. Patients were randomized in a 2:1 ratio to durvalumab or placebo. An independent data monitoring panel determined at an interim analysis that the study had met the primary PFS endpoint. The benefit/risk profile was also shown to favor the durvalumab arm. Overall survival continues to be evaluated.
Update Confirms Benefit of Encorafenib/Binimetinib Combo in Melanoma
The combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib reduced the risk of disease progression or death by 23% compared with single-agent encorafenib for patients with BRAF-mutant melanoma, according to findings from part 2 of the phase III COLUMBUS trial. The median progression-free survival for patients treated with the combination was 12.9 months compared with 9.2 months for patients receiving encorafenib alone (HR, 0.77; 95% CI, 0.61-0.97; P = .029).
Based on these data, along with previously reported findings from part 1 of the COLUMBUS trial, the developer of the combination, Array BioPharma, anticipates filing a new drug application with the FDA in June or July.
Atezolizumab Falls Short in Phase III Bladder Cancer Trial
Atezolizumab (Tecentriq) missed the phase III IMvigor211 trial’s primary endpoint of improving overall survival in the second-line setting for patients with locally advanced or metastatic urothelial carcinoma (mUC), according to Genentech, the manufacturer of the PD-L1 inhibitor. The IMvigor211 study was intended to confirm the findings of the phase II IMvigor210 study, on which the FDA based its May 2016 accelerated approval of atezolizumab as a treatment for patients with locally advanced or mUC whose disease progressed during or after platinum-based chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery.
Last month, atezolizumab received a second accelerated approval in bladder cancer, this time as a frontline treatment for cisplatin-ineligible patients with locally advanced or mUC. This indication was based on a different cohort from the IMvigor210 study than the initial second-line approval. The ongoing phase IMvigor130 study (NCT02807636) in this population is intended to support this accelerated approval. The news of the phase III IMvigor211 findings comes amid second-line bladder cancer approvals this month of 2 other PD-L1 inhibitors, avelumab and durvalumab.
Kite Reports Cerebral Edema Death in ZUMA-1 CAR T-Cell Trial
The first cerebral edema death in the ZUMA-1 chimeric antigen receptor (CAR) T-cell therapy trial was disclosed today by Kite Pharma on a conference call with investors announcing the company’s first quarter financial results. The patient was participating in a safety expansion of the phase II ZUMA-1 study of the anti-CD19 CAR T-cell therapy axicabtagene ciloleucel (KTE-C19; axi-cil). The trial is evaluating axicabtagene ciloleucel for the treatment of patients with relapsed or refractory aggressive non-Hodgkin lymphoma who are ineligible for transplant. The company completed enrollment of 30 US patients last month. Two patients have experienced grade 3 cytokine release syndrome (CRS).
The company said that 1 of those patients also experienced multiorgan failure and a neurologic event that progressed to a fatal cerebral edema that investigators determined was related to axicabtagene ciloleucel. Kite said that this patient had shown inadequate responses to both first- and second-line therapies, and had “rapidly progressive and symptomatic disease” at enrollment. This is the third death attributed to axicabtagene ciloleucel treatment in ZUMA-1. The company previously disclosed fatal incidents of hemophagocytic lymphohistiocytosis and cardiac arrest in the setting of CRS. A fourth death from pulmonary embolism was not related to treatment. In March, Kite applied for a biologics license application for axicabtagene ciloleucel based on preliminary results from ZUMA-1.