Alimta/Avastin Combo as Maintenance Therapy

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Alimta/Avastin Combo as Maintenance Therapy Looks Especially Good in AVAPERL Trial

http://blog.lungevity.org/2011/09/27/al ... inmaintrx/

September 27th, 2011 - by Dr. Jack West

The European Multidisciplinary Cancer Congress is just ending in Stockholm, and while I wasn’t there to see this presentation, we did just get word about the randomized phase 3 “AVAPERL” that were just reported there. This shows a very favorable result for the combination of Alimta (pemetrexed) with Avastin (bevacizumab) as maintenance therapy for advanced NSCLC patients who are eligible for Avastin and who hadn’t progressed following four cycles of cisplatin/Alimta/Avastin.

(Click blog link above to see image)

Specifically, with just the information included in the the press release, which at least conveys key highlights, 362 patients who hadn’t progressed after first line chemo with Avastin were randomized to one of two arms for maintenance therapy, one getting Avastin alone, and the other getting Alimta with Avastin. The arm getting the combination showed a significantly longer progression-free survival (PFS) starting from the beginning of all treatment, at 10.2 vs. 6.6 months (HR 0.50, p < 0.001), and also notable for being a numeric result for PFS that far exceeded the numbers we’ve seen from other first line trials, where PFS is typically in the 5-7 month range. There were no unexpected safety issues reported.

As mentioned above, 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 else included a group of patients who wouldn’t all be eligible for Avastin, who are more selected and tend to show the most favorable results overall. That said, the patient population in this trial is very comparable to the one in the ATLAS trial of maintenance Avastin vs. Avastin/Tarceva (erlotinib) after four cycles of first line chemo, which showed a median PFS of 4.8 months after first line chemo ended, or about 8 months from the beginning of all treatment.

Though many trials in the maintenance therapy setting have had their shortcomings in trial design (which tend to lead produce an greater suggested benefit from maintenance therapy than might be justified if everyone eventually received good treatment at some point), we’ve also seen a dramatic improvement in PFS and overall survival with Alimta in the JMEN trial, and now these results suggest that the combination of Alimta/Avastin as continuation maintenance is convincingly superior to Avastin alone.

Still, many experts have long 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 patients being randomized 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 we have more data from that trial, I’m personally impressed that the combination of Alimta/Avastin appears pretty impressive for patients who are eligible for it as a maintenance therapy strategy.