FDA News – July 2015

July 2015, Vol 6, No 6 - FDA Approvals, News & Updates

FDA’s Oncology Committee Says Necitumumab Shows Benefits in Metastatic Squamous NSCLC

The FDA’s Oncologic Drug Advisory Committee (ODAC) reviewed necitumumab (Eli Lilly & Co) for use in patients with metastatic squamous non–small-cell lung cancer (NSCLC). Necitumumab is an immunoglobulin G1 monoclonal antibody that inhibits the interaction between the human epidermal growth factor receptor (EGFR) and its ligands. EGFR expression is elevated in NSCLC and affects >95% of squamous NSCLC tumors.

ODAC members agreed that necitumumab showed benefits as first-line therapy in this patient population, based on the pivotal trial SQUIRE, which included patients with metastatic squamous NSCLC. Adding necitumumab to gemcitabine (Gemzar) plus cisplatin (Platinol) resulted in a 1.6-month improvement in median overall survival (OS) compared with the combination without necitumumab (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.74-0.96; P = .012) and a 0.2-month improvement in median progression-free survival (PFS; HR, 0.85; 95% CI, 0.74-0.98; P = .02).

No significant difference in overall response rate was observed between the 2 groups. In a second clinical trial, INSPIRE, the addition of necitumumab to the combination of pemetrexed (Alimta) plus cisplatin did not improve outcomes, including OS or PFS.

The majority of the panel members concluded that the drug shows a favorable risk–benefit profile, but certain safety concerns remain, such as a small and unexpected increase in mortality in patients taking the drug.

Necitumumab was associated with an increased risk for serious skin reactions, hypomagnesemia, and thromboembolic events. Furthermore, a small increase in the risk for sudden death was observed with necitumumab (2.2% vs 0.5% without the drug in SQUIRE, and 3.6% with necitumumab vs 1.6% without the drug in INSPIRE). The committee noted that thromboembolic events have recently been reported with current monoclonal antibodies used in patients with squamous NSCLC.

The committee notes that careful consideration is needed when using ­necitumumab in combination with platinum in patients with a history of cor­onary artery disease, congestive heart failure, or arrhythmia. Close monitoring of serum electrolytes is also necessary.

Necitumumab also was less effective in patients aged >70 years; some panelists urged the company to recommend against the use of necitumumab in patients in this age-group.

According to the summary of the discussion by ODAC, the FDA’s Division of Oncology Products is looking for advice from ODAC regarding the biologic drug application for necitumumab on 2 issues. The first is whether the efficacy and safety results from SQUIRE in patients with squamous NSCLC support a positive benefit–risk ratio for the addition of necitumumab to the combination of gemcitabine and cisplatin. The second is whether the results from the INSPIRE trial in patients with nonsquamous NSCLC affect the benefit–risk ratio of necitumumab in patients with squamous NSCLC.

Although the committee did not make a final recommendation to the FDA, the positive feedback suggests that the FDA will likely approve the drug in the next few months. (July 9, 2015)