Pfizer's lung cancer drug Xalkori adds rare gene treatment

Pfizer's drug for lung cancer driven by a rare gene, Xalkori, has been FDA granted approval to treat an even rarer genetic sub-type.

Xalkori (crizotinib) was first approved in 2011 for patients with the ALK+ gene mutation, which occurs in between 1 and 7% of patients with non-small cell lung cancer (NSCLC).

On Friday the company announced the FDA had granted an additional licence for the drug against ROS1+ patients through its Breakthrough Therapy Designation.

The ROS1 gene plays a role in just 1% of the estimated 1.5 million new cases of NSCLC cases every year. Pfizer's drug has shown early signs that patients could live longer without the disease progressing.

The ROS1 gene attaches to another gene, a 'rearrangement' which changes the way each gene normally functions, which can contribute to cancer-cell growth.

Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology said the approval was an important milestone. It makes the drug the only FDA-approved biomarker-driven therapy for two distinct molecular targets in metastatic NSCLC.

The FDA approval is based on a multicentre, single-arm Phase 1 study (Study 1001) of 50 patients with ROS1-positive metastatic NSCLC treated with 250 mg of XALKORI orally twice daily. The efficacy outcome measures in this study were objective response rate and duration of response.

The study showed an objective response rate of 66% by an independent radiology review. There was one complete response and 32 partial responses. The median duration of response was 18.3 months (95% CI: 12.7 months, not reached).

Xalkori produces a long list of potential side-effects and adverse events in patients in ALK+ patients, and a similar pattern was seen in ROS1+ patients.

Serious adverse events were reported in 34% of patients treated with XALKORI, the most frequent were dyspnea (4.1%) and pulmonary embolism (2.9%).

Less serious but more common were vision disorders, which occurred at far higher levels than in patients on chemotherapy. They occurred in 92% of patients in the ROS1 study; 90% of patients had Grade 1 vision disorders and 2% had Grade 2.

Pfizer estimates that 15,000 patients may be driven by oncogenic ROS1 fusions. However Xalkori has only been used in around 8,000 patients so far (those who are ALK+) illustrating the difficulty in identifying these patients.

Moreover a companion diagnostic to identify the ROS1+ patients is still in development, which means doctors will have to rely on lab tests to uncover cases until it is developed and approved.

The rarity of the patients and these factors have kept Xalkori's sales low – in 2015 it earned just £111 million, although this was a 26% increase on the previous year.

Novartis' Zykadia (ceritinib) was approved in 2014 in the US and last year in Europe for patients with ALK+ NSCLC previously treated with Xalkori.