FDA Approves PORTRAZZA® for Metastatic Squamous Non-Small Cell Lung Cancer

SUMMARY: The FDA on November 24, 2015, granted approval to Necitumumab (PORTRAZZA®) in combination with GEMZAR® (Gemcitabine) and Cisplatin for the first line treatment of patients with metastatic Squamous Non Small Cell Lung Cancer (NSCLC). Lung cancer is the second most common cancer in both men and women and accounts for about 13% of all new cancers and 27% of all cancer deaths. It is the leading cause of cancer death among both men and women. The American Cancer Society estimates that over 221,200 new cases of lung cancer will be diagnosed in the United States in 2015 and over 158,000 patients will die of the disease. Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Of the three main subtypes of Non Small Cell Lung Cancer (NSCLC), 30% are Squamous Cell Carcinomas (SCC), 40% are Adenocarcinomas and 10% are Large cell carcinomas.

Epidermal Growth Factor Receptor (EGFR) a Receptor Tyrosine Kinase (RTK) has been long known to control malignant cell proliferation, growth, survival, metabolism and migration. Therefore targeting EGFR with monoclonal antibodies has proven to be an effective strategy for the treatment of cancer. The two EGFR targeted monoclonal antibodies that have been available in the US include ERBITUX® (Cetuximab-chimeric IgG1) and VECTIBIX® (Panitumumab-human IgG2). PORTRAZZA® is a human IgG1 monoclonal antibody which also binds to the human Epidermal Growth Factor Receptor and blocks the binding of EGFR to its ligands.

The approval of PORTRAZZA® was based on the results of an open label, multicenter, multinational, phase III trial in which treatment naïve patients with metastatic Squamous NSCLC (N=1093) were randomized to receive PORTRAZZA® in combination with GEMZAR® (Gemcitabine) and Cisplatin (N=545) or GEMZAR® and Cisplatin alone (N=548). Treatment consisted of either PORTRAZZA® 800 mg IV days 1 and 8, GEMZAR® 1250 mg /m2 IV on days 1 and 8 along with Cisplatin 75mg/m2 IV on day 1 of each of a 21 day cycle or GEMZAR® and Cisplatin alone. Both treatment groups were well balanced and median age of patients was 62 years. The primary endpoint was Overall Survival and secondary endpoints included Progression Free Survival (PFS) and Overall Response Rate (ORR).

At a median follow up of 25 months, the median OS was 11.5 months in the PORTRAZZA® group and 9.9 months in the chemotherapy alone control group (HR = 0.84; P=0.01). The median PFS was 5.7 months in the PORTRAZZA® group and 5.5 months in the control group (HR=0.85; P=0.02). There was no difference in ORR noted in the two treatment groups (31% vs 29%). More patients in the PORTRAZZA® group experienced skin rash and hypomagnesemia and patients will therefore require close monitoring of serum electrolytes.

The authors concluded that the addition of PORTRAZZA® to GEMZAR® and Cisplatin chemotherapy significantly improves Overall Survival in patients with advanced Squamous NSCLC and represents a new first line treatment option for this malignancy. Because of the lack of benefit, PORTRAZZA® is not indicated for the treatment of non-Squamous NSCLC. 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. Thatcher N, Hirsch FR, Luft AV, et al. Lancet Oncol. 2015;16:763-774