As described in my last post, one of the interesting points we've seen from the recent trial of maintenance alimta vs. placebo after first line chemo for advanced NSCLC is that alimta's beneficial effects appear to be concentrated on the 2/3 of patients with non-squamous cancers, while the patients with squamous cell NSCLC did no better with alimta than with placebo. That post also described how sensitivity to alimta may be associated with low levels of a relevant target enzyme for alimta, called thymydylate synthetase (TS), and that TS levels are relatively high in squamous cell NSCLC, and also in SCLC.

Unfortunately, the results of a large trial in extensive SCLC (abstract not yet available on ASCO website) clearly confirmed that alimta isn't an improvement as a treatment for SCLC. This trial was designed to directly compare the regimen of carboplatin/alimta to carboplatin/etoposide, which is a standard regimen for this setting. It was designed to enroll 1820 patients (!) and look for a significant improvement in survival. The study had enrolled 733 patients when the "Data Safety Monitoring Board", which reviews results during the conduct of a trial to ensure that one arm isn't doing so remarkably well or poorly that it would be unethical to continue to randomize patients, found that the carbo/alimta arm was doing so poorly that it was not possible that it would ever emerge as superior. It was closed, and Dr. Socinski presented the results.

In pretty much every measure, the carbo/alimta arm fared worse than the arm receiving standard carbo/etoposide. Median progression-free survival was 3.7 vs. 5.3 months, and the survival curve shows the dramatic difference:

The other measures supported the same conclusion. The median overall survivals with carbo/alimta vs. carbo/etoposide were 7.3 vs. 9.6 months, and response rates were 25% vs. 40%. Even side effects, usually a very strong suit for an alimta regimen, didn't look better than carbo/etoposide, and in some measures like degree of anemia and need for transfusions, the carbo/alimta regimen was significantly worse.

There isn't too much more to say about it, except that it was remarkably convincing that there was nothing to recommend alimta in the setting of SCLC. It certainly deserved to be tested, and this regimen had looked promising in smaller earlier trials in SCLC, but it was one of the most definitive answers you could ever see. While we've become quite impressed with its value in NSCLC, and from now on perhaps particularly in those patients with non-squamous cancers, I would say that alimta doesn't have much of a future in SCLC. On the other hand, the results looked favorable enough for the regimen of carbo/etoposide, which is reassuring to see when we'd like to consider it as a kinder, gentler alternative to cisplatin/etoposide for ED-SCLC. So perhaps there was still some positive that came out of this otherwise disappointing trial.