An international, multi-institutional study, presented at the American Society of Clinical Oncology 2009(ASCO), finds that use of pemetrexed (Alimta) as maintenance therapy following standard treatment improves overall survival for patients with advanced non-small cell lung cancer (NSCLC); the study also further confirms that this benefit is primarily limited to those with the nonsquamous subtype.

The efficacy, tolerability and ease of administration provided a strong rationale for evaluating pemetrexed as maintenance therapy in patients with advanced non-small cell lung cancer whose cancer had not progressed following four cycles of platinum-based chemotherapy. The drug was given on an ongoing basis until patients’ disease progressed.

"This study will change the overall standard of care," said Dr. Chandra P. Belani, Deputy Director of the Penn State Cancer Institute and the study’s lead author. "Maintenance therapy with pemetrexed offers a new paradigm for patients who have advanced lung cancer, because it has a low toxicity and can be given on an ongoing basis over a prolonged period of time to extend patients’ lives."

Pemetrexed is currently approved as a first-line treatment for advanced nonsquamous non-small cell lung cancer in combination with the chemotherapy agent cisplatin and as a single agent in patients with recurrent disease. Preliminary results of the current study presented at the 2008 ASCO Annual Meeting had demonstrated that maintenance therapy with pemetrexed delayed disease progression, but this is the first time a significant improvement in overall survival has been shown in this setting.

In this randomised, double-blind, phase III study, patients were given either pemetrexed (441 patients) or placebo (222 patients), along with the best supportive care. All patients had advanced or metastatic (stage 3B or 4) NSCLC (both squamous and nonsquamous subtypes) that had not progressed after four cycles of platinum-based chemotherapy.

Patients who received pemetrexed had an overall survival of 13.4 months, versus 10.6 months for patients in the placebo group. For the nonsquamous subgroup (482 patients), overall survival was 15.5 months for patients on pemetrexed, versus 10.3 months for patients on placebo. Patients with the squamous subtype do not seem to benefit with pemetrexed, confirming what has been shown in other studies. Researchers suspect the possible mechanism for this difference in effectiveness may be related to the expression of biomarkers such as thymidylate synthetase, which has been shown to correlate with sensitivity to pemetrexed.

Severe (grade 3 or 4) side effects were low but more common in the pemetrexed group, specifically fatigue (five per cent in the pemetrexed group, versus 0.5 per cent in the placebo group) and low white blood cell counts (2.9 per cent versus 0 per cent). Side effects did not increase for patients who received pemetrexed for a longer period of time, and there were no drug-related deaths.