I'm at Swedish Hospital, not in Stockholm, Sweden now, where the European Multidisciplinary Cancer Congress is going on. But there, the preliminary results of the AVAPERL phase III randomized trial were just reported, and they certainly look encouraging for the combination of Alimta (pemetrexed) and Avastin (bevacizumab) as a maintenance therapy for patients with Avastin-eligible advanced NSCLC who hadn't progressed after four cycles of cisplatin/Alimta/Avastin, compared with maintenance Avastin alone.

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As I mentioned, I don't have all of the details from the presentation, really just the press release, which at least conveys some highlights. As shown above, a total of 362 patients who hadn't progressed after first line chemo/Avastin were randomized to either of the two maintenance therapy arms, and the combination arm showed a significantly longer progression-free survival (PFS) counting from the beginning of all treatment, at 10.2 vs. 6.6 months (HR 0.50, p < 0.001), but also a numeric result for PFS that far exceeded the numbers we've seen from other first line trials, where PFS has generally been in the 5-7 month range. There were no unexpected safety issues, but otherwise, I don't have other details.

Importantly, this trial enrolled only Avastin-eligible patients who hadn't progressed or shown prohibitive toxicity issues after the first four cycles of treatment. Most other trials that we might compare these results to included all patients starting from the beginning of first line therapy, or included a group of patients who weren't all eligible for Avastin -- this group being more selected and tending to show more favorable results. But this trial population is very comparable to the one in the ATLAS trial of maintenance Avastin vs. Avastin/Tarceva (erlotinib) after four cycles of first line chemo, and that trial showed a median PFS of 4.8 months after first line chemo was completed, so about 8 months after the start of all therapy.

Though many of these maintenance therapy trials have had their shortcomings in trial design (that have tended to lead to an overstatement of the benefits of maintenance therapy), the improvement in PFS and overall survival with Alimta in the JMEN trial is quite dramatic, and these results suggest that the combination of Alimta/Avastin as continuation maintenance is convincingly superior to Avastin alone. However, many of us have suspected that maintenance Avastin on its own may not be an especially effective therapy, and at this point it remains to be seen whether the combination of Alimta/Avastin is actually significantly superior to Alimta alone. This question should be answered by the important, ongoing ECOG 5508 trial (carboplatin/Taxol (paclitaxel)/Avastin for four cycles followed by randomization of nonprogressing patients to maintenance Alimta alone, Avastin alone, or the Alimta/Avastin combination). But we'll be waiting on that trial for a couple more years.

Until then, I've got to say that the Alimta/Avastin combination looks pretty impressive for patients who are eligible for it as a maintenance therapy strategy.