Portrazza FDA approved for Advanced Squamous NSCLC

The combination of Portrazza (necitumumab) with gemcitabine and cisplatin has been FDA approved as first-line therapy for patients with locally advanced or metastatic squamous non-small-cell lung cancer (NSCLC). The approval is based on findings from the phase III SQUIRE trial.

The combination of Portrazza (necitumumab) with gemcitabine and cisplatin has been FDA approved as first-line therapy for patients with locally advanced or metastatic squamous non-small-cell lung cancer (NSCLC). The approval is based on findings from the phase III SQUIRE trial.

In the 1093-patient study, the addition of the fully human IgG1 anti-EGFR monoclonal antibody Portrazza to gemcitabine and cisplatin improved overall survival (OS) by 1.6 months, which was equivalent to a 16% reduction in the risk of death. Progression-free survival (PFS) was improved by 15% with the triplet therapy.

The FDA approval follows an informal recommendation from the Oncologic Drugs Advisory Committee in July 2015. Following a discussion on the clinical trial results from the SQUIRE trial, the consensus of the panel was that the benefits of Portrazza were modest, yet clinically significant.

"Lung cancer is an extremely complicated disease that requires a variety of therapy options so doctors can choose an appropriate treatment for each patient's unique circumstances," said

Bonnie J. Addario

, founder and chair of the

Bonnie J. Addario Lung Cancer Foundation

, and a lung cancer survivor. "Today's approval represents progress for patients diagnosed with metastatic squamous non-small cell lung cancer, as each new therapy advances cancer care and gives patients hope for improved outcomes."

In the phase III study, patients were randomized to receive gemcitabine plus cisplatin with Portrazza (n = 545) or placebo (n = 548). Portrazza was administered at 800 mg on day 1 and 8 every 3 weeks. In both arms, gemcitabine was administered at 1250 mg/m2 on days 1 and 8 and cisplatin was administered at 75 mg/m2 on day 1. Those who responded in the investigational arm went on to receive single-agent Portrazza.

Baseline characteristics were balanced between the two arms. The median age of patients was 62 years, the majority of patients were white (84%), and most had smoked (91%). The most frequent metastatic site was the lung (83%). The primary endpoint of the study was OS, with secondary outcome measures focused on progression-free survival (PFS) and objective response rate (ORR).

After a follow-up of approximately 25 months, the median OS was 11.5 months in the Portrazza arm versus 9.9 months with the chemotherapy alone (HR = 0.84; 95% CI, 0.74-0.96; P = .012). The 1-year OS rate was 48% versus 43% and the 2-year OS rate was 20% compared with 17%, for the Portrazza and chemotherapy arms, respectively.

The median PFS with Portrazza was 5.7 versus 5.5 months for chemotherapy alone (HR, 0.85; 95% CI, 0.74-0.98; P = .02). The PFS rate at 6 months was 45% with Portrazza and 37% with chemotherapy alone.

The ORR was 31% in the Portrazza arm and 29% with the chemotherapy alone (P = .40). The disease control rate (ORR plus stable disease) was 82% in the Portrazza group compared with 77% in the chemotherapy arm (P = .043). The median time to treatment failure with Portrazza was 4.3 months versus 3.6 months with chemotherapy alone.

Grade ≥3 adverse events (AEs) were apparent in 72% of patients treated with Portrazza versus 62% with chemotherapy alone. Grade ≥3 AEs that occurred significantly more often in the Portrazza /chemotherapy arm were hypomagnesemia (9% vs 1%), skin rash (4% vs <1%), and venous thromboembolic events (5% vs 3%).

Serious AEs occurred in 48% of patients in the Portrazza arm versus 38% with gemcitabine and cisplatin alone. Adverse events leading to discontinuation of treatment occurred at a rate of 31% in the Portrazza /chemotherapy arm and 25% in the chemotherapy alone arm. The incidences of adverse events with an outcome of death were 12% and 11%, respectively.

"The SQUIRE trial is the largest trial reported for patients with advanced squamous cell carcinoma, and the therapeutic options that we do have are very limited," study author Martin Reck, MD, PhD, Head of Thoracic Oncology, Hospital Grosshansdorf, said at the 2015 ASCO Annual Meeting, when updated data were presented. "We observed a significant improvement in overall survival and progression-free survival in favor of the combination with necitumumab."

Lilly is offering assistance programs for eligible patients receiving Portrazza, including a copay program that allows qualified patients to pay no more than $25 per dose. For more information, contact The Lilly Answers Center at 1-800-545-5979 or visit www.lilly.com.

A phase I/II study is currently assessing Portrazza in combination with gemcitabine and cisplatin as a first-line therapy for patients with stage IV squamous NSCLC. The primary endpoint of the first portion of the study is dose-limiting toxicities (NCT01763788). Additionally, trials are planned to assess different chemotherapeutics in combination with Portrazza, including nab-paclitaxel and carboplatin (NCT02392507).

Thatcher N, Hirsch FR, Luft AV, et al. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015;16(7):763—774.