Pfizer’s investigational agent PF-00299804 has shown an ability to prevent disease progression when given as a first-line treatment in patients with advanced non-small cell lung cancer.

Preliminary results from an ongoing Phase II trial showed that nearly 85% of patients whose cancers harboured mutated forms of the EGFR gene have remained progression-free for at least nine months, according to Tony Mok from the Chinese University of Hong Kong.

The drug (also known as PF-299) is an oral, once-daily, pan-HER (pan-human epidermal growth factor receptor) inhibitor that irreversibly inhibits several members of the HER family, including HER 1(EGFR), HER-2 and HER-4. Drugs such as Roche's Tarceva (erlotinib) and Astra Zeneca's Iressa (gefitinib) have been shown to be effective against cancer in patients with a mutation activating just EGFR.

Dr Mok said that PF-299 is of great interest because it targets multiple receptors on the HER pathway. “It also inhibits signalling in both wild-type and mutant EGFR, including forms of NSCLC that are resistant to EGFR inhibitors such as erlotinib and gefitinib," he added.

The phase II trial includes patients with advanced non-small cell lung cancer and no prior systemic treatment for their disease. All were either non-smokers or light smokers, or were known to have EGFR mutations.

The initial results showed that patients received either once-daily 30mg or 45mg of PF-299. Nine months later, 57.1% of the overall group and 84.7% of those with EGFR mutations remained progression-free.

Another study presented at the European Society for Medical Oncology congress in Milan showed that PF299 was better than erlotinib in a randomised head-to-head Phase II study in patients with advanced NSCLC who had progressed on at least one prior chemotherapy regimen. The trial involving 188 patients randomised to either 150 mg QD erlotinib or 45 mg PF-299 found that PF-299 resulted in significant improvement in progression-free survival relative to erlotinib (median PFS 12.4 weeks versus 8.3 weeks, respectively).

The efficacy advantage for PF-299 was even more striking for wild type KRAS patients and a Phase III study of PF-299 versus erlotinib for second-/third-line therapy of advanced NSCLC is planned. 

Rhonda Siddall in Milan