European Commission authorises necitumumab (Portrazza) for advanced squamous non-small cell lung cancer

Eli Lilly and Company has announced that the European Commission has granted a marketing authorisation for necitumumab (Portrazza^TM), for use in combination with gemcitabine and cisplatin chemotherapy for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) expressing squamous non-small cell lung cancer (NSCLC) who have not received prior chemotherapy for this condition. Necitumumab is the first biologic licensed in the EU as a first-line treatment option for this indication. ^1,2

"Today's news means that EU patients have a new first-line treatment option for this difficult-to- treat form of lung cancer. Lung cancer is the leading cause of cancer death in the EU and there is a need for first-line treatment options, especially for squamous non-small cell lung cancer, which currently has a five-year survival rate of less than five percent for patients with metastatic disease."³ said Richard Gaynor, M.D., senior vice president of product development and medical affairs for Lilly Oncology.

"Little progress has been made in the treatment of squamous non-small cell lung cancer in the first- line setting in the past two decades." Said Nick Thatcher, Professor of Medical Oncology at Christie Hospital Manchester. "Nearly a third of lung cancer patients have this specific, difficult-to-treat type of cancer and a new treatment option will be welcomed by the doctors who are caring for them."

This authorisation is based on the results of the "SQUIRE" trial, an open-label, randomised, multi- center Phase III trial that compared first-line treatment with necitumumab in combination with gemcitabine and cisplatin to treatment with gemcitabine and cisplatin alone in patients with advanced squamous NSCLC. This is the first authorisation for necitumumab in Europe and follows U.S. Food and Drug Administration (FDA) approval in November 2015.

About Necitumumab (Portrazza^TM)

Necitumumab (Portrazza^TM) is a recombinant human IgG1 monoclonal antibody that is designed to block the ligand binding site of the human epidermal growth factor receptor 1 (EGFR). Activation of EGFR has been correlated with malignant progression, induction of angiogenesis and inhibition of apoptosis, or cell death. As demonstrated in preclinical studies, EGFR plays a role in the formation (tumourigenesis) and spread (metastasis) of tumours.⁴

About the "SQUIRE" Trial

"SQUIRE" was an open-label, randomised, multi-center Phase III trial that compared first-line treatment with necitumumab in combination with gemcitabine and cisplatin to treatment with gemcitabine and cisplatin alone in patients with metastatic squamous NSCLC. The main outcome measure, or primary endpoint, was overall survival. Median overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group (median 11·5 months [95% CI 10·4-12·6]) vs 9·9 months [8·9-11·1]; stratified hazard ratio 0·84 [95% CI 0·74-0·96; p=0·01]). ^{2, 5}

The SQUIRE study was conducted across 184 investigative sites in 26 countries⁵ and enrolled 1,093 people with stage IV squamous NSCLC. Of those enrolled, 90 percent had metastatic disease at two or more sites, indicating a high metastatic disease burden for the majority of these patients. Nearly 90 percent of patients in the SQUIRE study were assessable for EGFR protein expression by immunohistochemistry (IHC). Of these, more than 95 percent of patients had EGFR expressing tumours.²

Thromboembolic events and cardiorespiratory disorders are the most important risks associated with Portrazza. This information is important for the safe use of Portrazza and physicians/oncologists are required to consider this before treatment is initiated.⁶

The most common adverse events in SQUIRE (≥ 10 %) were: vomiting, stomatitis, skin reactions, pyrexia, hypomagnesaemia, albumin-corrected hypocalcaemia, hypophosphatemia, hypokalemia and weight decrease.²

About Squamous Non-Small Cell Lung Cancer (NSCLC)

NSCLC is the most common type of lung cancer, and accounts for about 80 percent of all lung cancer cases.⁷ Squamous NSCLC, which represents about 30 percent of all lung cancer cases, is a devastating, difficult-to-treat form of the disease.^5,8,9,10 Patients face an imposing disease and symptom burden with very poor prognosis; the five-year survival rate for patients with metastatic disease is less than five percent.³ In the first line treatment setting, little progress has been made over the past two decades, leaving a significant unmet medical need.¹¹