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Alimta for Brain Metastases in NSCLC?
Dr. Garfield

Brain metastases from NSCLC is almost a field of its own. This is because of the relatively high frequency with which metastases appear, the fact that they may return, even after treatment with whole brain radiation therapy (WBRT), and that our chemotherapy has long been considered to be ineffective against them. In fact, the extent of them as a problem is reflected in the number of thread questions on this subject in the GRACE forum. At the same time, there has also been work devoted to prophylactic whole brain radiation therapy (WBRT) in selected NSCLC patients considered to be at high risk. For unknown reasons, adenocarcinomas (ADC) seem to be the most likely to appear in the brain, at times the first/only site outside of the lung.

For this reason, a recent study of Alimta, published on-line in Lung Cancer, by Bearz and colleagues from several hospitals in Italy, may be of interest. Of a subset of 22 patients with brain metastases who either recurred after WBRT (11 patients) or had never received radiation (11 patients), and then received Alimta (pemetrexed), a remarkable 68% had what the authors called a “cerebral benefit.” Of the 22, 5 had a partial response, 9 had stable disease, while only 7 had progressive disease.

That being said, the study had several limitations. First, although half of the 22 had prior WBRT, the authors did not say how each of the 2 groups fared. The implication is that some of the 14/22 who benefited from Alimta had prior WBRT. Next, it would have been good to see how those few with squamous cell carcinomas (SCC) responded. In the entire group of 39 patients, only 4 had SCC, a subtype not generally felt to respond well to Alimta. Finally, this was a small study, with presumably a relatively homogeneous population, and the results may not reflect what might happen elsewhere. On the other hand, of the 39 patients with brain mets treated with Alimta, the median survival was 10 months, a pretty encouraging result considering what we had historically expected.

Clearly, more pre-clinical work needs to be done to determine the factors leading to central nervous system penetration by this drug. However, since we are loath to re-radiate the brain in such patients, this may be a strong alternative for those who progress after prior radiation. Also, since these patients are often somewhat frail, and Alimta is often quite well tolerated, the drug is appealing (it is already approved as second-line and maintenance chemotherapy as a single agent). Finally, in patients with locally advanced disease receiving combined radiation and chemotherapy, one might consider Alimta to go along with a platinum, at least in those with ADCs.

We hope to see further work on this subject, since it certainly represents an unmet need in lung cancer management.

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