ODAC discusses necitumumab for squamous NSCLC but takes no action

An FDA advisory committee today generally expressed support for the approval of necitumumab for the first-line treatment of patients with locally advanced or metastatic squamous non–small cell lung cancer.

However, the Oncologic Drugs Advisory Committee decided not to formally vote. The committee members gave no specific explanation regarding their decision not to vote; but, they stated their discussion provided sufficient information on the risk–benefit profile.

In the phase 3 SQUIRE trial, the addition of necitumumab (Eli Lilly) — a second-generation monoclonal antibody — to gemcitabine and cisplatin significantly improved OS as first-line treatment for patients with squamous NSCLC (11.5 months vs. 9.9 months; P < .001).

Necitumumab also conferred a 0.2-month median PFS improvement, which met statistical significance (5.7 months vs. 5.5 months; P = .02).

However, patients assigned necitumumab experienced high rates of serious adverse events (48% vs. 38%), including an increased risk for potentially fatal venous thromboembolism.

The incidence of grade 3 or worse thromboembolic events was 9% in the necitumumab arm vs. 5% in the gemcitabine and cisplatin arm. The most common venous thromboembolic events — some of which were fatal — included pulmonary embolism and deep vein thrombosis. The most common arterial thromboembolic events included myocardial infarction and cerebrovascular accidents.

Some panelists also expressed concern that American patients comprised only 6% of the study population.

The FDA’s Oncologic Drugs Advisory Committee reviewed the results of the SQUIRE trial prior to today’s session.

“Approval from a single trial needs to be based on robust and compelling evidence of clinical benefit,” Brent Logan, PhD, professor and director of the division of biostatistics at the Medical College of Wisconsin and a temporary voting member of ODAC, said during the meeting. “I think that survival is a compelling endpoint. … OS allows us to weigh the benefit and the risk very clearly. I think that patients may be willing to risk these toxicities for a survival benefit.”

Other panelists expressed that the present data do not justify approval of the drug at this time.

“There are still caveats regarding toxicity and, to some degree, the magnitude of the overall benefit,” Michael E. Menefee, MD, assistant professor of medicine at the Mayo Clinic in Jacksonville, Florida, and a voting member of ODAC, said. “The additional studies that are evaluating this compound in this patient population bear significant impact on whether or not the results of this study are valid.”

The FDA typically follows the advisory committee’s recommendations but is not obligated to do so. Although the panel did not cast a vote, a formal FDA decision related to the approval of necitumumab will be reached on or before the official deadline later this year, according to the panel.

"We are encouraged by the Committee's constructive discussion on the benefit–risk profile of necitumumab, as few advances have been made over the past two decades in the first-line treatment of advanced squamous NSCLC, leaving a significant unmet medical need," Richard Gaynor, MD, senior vice president, product development and medical affairs for Lilly Oncology, said in a statement released after the session. "We believe necitumumab with gemcitabine and cisplatin represents a meaningful advance in the search for a new first-line treatment option and look forward to working closely with the FDA as they continue their review." – by Cameron Kelsall