It's been two and a half years since I described a phase IIB trial of Fotolyn (pralatrexate), a relatively new chemotherapy agent, being compared to Tarceva (erlotinib) in current or ex-smokers with previously treated advanced NSCLC. The new drug, Fotolyn, is described in a prior post, and it has since been approved by the FDA as a treatment for peripheral T-cell lymphomas, so it's commercially available in the US. Today, Allos Therapeutics, the company that makes Fotolyn, sent out a press release that the clinical trial is positive for a modest survival advantage vs. Tarceva in this trial of current and former smokers. A total of 201 patients were enrolled, with a 13% improvement in OS in the overall population (166 included for analysis). In addition, there were some predefined patient groups for subset analysis, which demonstrated that light smokers (I don't have the precise definitions for light vs. heavy smoking history) did particularly better with Fotolyn (HR 0.63, corresponding to a 37% improvement), as did patients with non-squamous cancers (HR 0.65, corresponding to a 35% improvement). They saw trends in favor of Fotolyn for overall survival in all groups except those with squamous NSCLC and those who received prior Alimta (pemetrexed).

The other side of the coin is drug safety, which showed that mucositis (mouth sores) were moderate to severe in 23% of patients, and other common but typically relatively mild side effects included decreased blood counts (expected with just about all standard chemo agents), fatigue, and shortness of breath (which may have been more from the underlying cancer). These results are certainly interesting and fairly promising. We would expect that Tarceva's benefit is not very strong in current smokers or those with a significant smoking history, but Fotolyn didn't beat Tarceva in heavy smokers, nor was it convincingly better in patients with squamous NSCLC, a group that we think of as receiving pretty minimal to modest benefit with Tarceva. It's also not clear whether there is anything to the subset analysis that showed no benefit of Fotolyn over Tarceva in patients who received prior Alimta. This wasn't a large trial, and subset analyses, especially in small trials, can sometimes randomly show differences that aren't really real, or miss differences that actually exist, because small sample groups are unreliable. I presume that Allos will pursue in moving Fotolyn forward in NSCLC, in terms of getting FDA approval; this randomized phase IIB trial, very much designed like an underpowered phase III trial, is ostensibly enough to move forward with a larger trial that can lead to FDA approval. The lack of mention of P values in the press release leads me to presume that differences are not significant, but I'm sure we'll learn more once the results of this trial are presented in an upcoming meeting. In the meantime, it's possible that this will lead to some use of Fotolyn in NSCLC patients, at least those with a smoking history, but I expect that getting it covered by insurance may be challenging until we have more data. At the very least, this is a promising lead as a new option to hope to see for current or previously smoking patients with previously treated advanced NSCLC.