It was nearly three years ago when the results of a randomized phase III trial of the chemotherapy agent Javlor (vinflunine) compared with standard second line Taxotere (and its proven survival benefit in previously treated advanced NSCLC), both drugs given IV every three weeks. I summarized the results of that trial shortly after the ASCO meeting in 2007, but to be honest, I didn't even remember if I had done that. Javlor has barely been spoken of since then. The results showed completely equivalent efficacy and some greater GI side effects with Javlor, including constipation, abdominal pain, and nausea in the Javlor arm (though more hair loss with Taxotere). In contrast, Alimta (pemetrexed) had recently been shown to have equivalent efficacy but a modestly better side effect profile, at least in terms of blood counts dropping. Over time, Alimta became a leading second line option, while Javlor hasn't been submitted for FDA approval and hasn't generated much discussion as a treatment option thus far.

While I was among the many people who gave a collective yawn when the results were presented from the trial of Javlor vs. Taxotere, it's now three years later (a much longer interval than what you'd see for more eagerly discussed findings), and the results are being published in the Journal of Clinical Oncology, still showing completely superimposable efficacy results.

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The results aren't any better, but at this point I'm much more inclined to see the glass as half full than half empty, and I'd be eager to have this agent available for my patients. What's changed over the past three years?

Essentially, we now have more patients living longer and running out of treatment options with any anticipated benefit before they run out of functional capacity to benefit from them. When the Javlor trial was initially presented in 2007, our best understanding was that Alimta was an equally appropriate choice for patients with squamous as well as non-squamous NSCLC, but we've since learned that Alimta is not active in squamous NSCLC and is specifically noted to not be approved for this population. This means that patients with squamous NSCLC, who are not routinely given Avastin (due to safety concerns) are also not eligible for Alimta, and the well studied treatment options for previously treated advanced NSCLC of squamous histology are now limited to Taxotere or Tarceva (and some patients will have already received Taxotere in the first line setting). Meanwhile, the evolving shift toward maintenance therapy after 4-6 cycles of first line treatment means that more patients will start one of these agents earlier. Functionally, this is likely to mean that more patients will have an extra line of treatment squeezed in, and they'll be earlier to reach a point where they run out of treatment options that have been studied and appear effective in the setting of previously treated NSCLC.

Meanwhile, even though patients with adenocarcinoma/nonsquamous NSCLC still have Alimta available, the ground has also been shifting for this population as well. Alimta has now been FDA approved as a first line therapy for these patients and is increasingly used early, leaving it unavailable or at least less appealing as a later option. And with maintenance therapy also exhausting treatment options a little earlier, and also with more patients living longer (a very good thing), we're seeing plenty of patients with nonsquamous NSCLC also exhausting the well studied, common treatment options after having received prior treatment.

It's true that this trial doesn't address treatment in the third or fourth line setting, but we routinely fall back to the short list of treatments that have shown efficacy in previously treated NSCLC. Now that there's a greater need for additional tools as patients are getting more of an opportunity to benefit from additional treatments, I'd be happy to have it available and would definitely recommend it for some of my patients. I'd prefer to have agents with a more favorable side effect profile and efficacy equal to (or especially superior to) a standard like Taxotere, but we still need more feasible agents that are proven options for patients who have already received prior chemotherapy.