Continuation Maintenance Therapy with Alimta/Avastin

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Continuation Maintenance Therapy with Alimta/Avastin: Details on the AVAPERL Trial

http://blog.lungevity.org/2011/12/24/av ... n-maintrx/

December 24th, 2011 - by Dr. Jack West

Earlier this year, I described the preliminary reported results from the AVAPERL trial, enrolling patients with first line treatment of advanced nonsquamous NSCLC with four cycles of cisplatin/Alimta (pemetrexed)/Avastin (bevacizumab), then assigned patients who hadn’t progressed to either four cycles to either maintenance Alimta/Avastin or Avastin as a single agent. At the 2011 meeting of the European Society for Medical Oncology (ESMO), the investigators (Barlesi and colleagues) presented early results revealing a very significant improvement in progression-free survival (PFS) from the beginning of treatment (from the time of starting first line), at 10.2 vs. 6.6 months (HR 0.50, p < 0.001), as shown in the figure below:

(Click on the blog link above to view the images)

Looking at the results plotted from the time of randomization to combination vs. single agent Avastin as maintenance therapy provides an even more striking distinction between the two arms:

Back in September, I didn’t have any information about overall survival (OS), but here’s the preliminary OS results, with numbers from the time of starting all treatment:

While these results are preliminary, the difference of a 25% better OS with continuation of Alimta is impressive to me, especially considering that the arm that received maintenance Avastin alone, while the inferior arm here, has a median survival of nearly 16 months: we would consider that result to be excellent in the context of other advanced NSCLC trials (for instance, 12 months for cisplatin/Alimta on one large phase III randomized trial, 12 months with carboplatin/Taxol (paclitaxel) with Avastin in another). So we can’t say that the Avastin alone arm underperformed — it did quite well, but the Avastin/Alimta arm did remarkably well.

So I take these results to support the following key conclusions:

1) Maintenance Avastin on its own may or may not add some meaningful benefit, but adding another agent with good activity against NSCLC (at least Alimta) is likely better. Whether the Avastin is actually anything will be tested directly in the ECOG 5508 trial that is ongoing now.

2) Clearly the value of the Alimta hasn’t been exhausted by continuing it after four cycles of initial therapy in the first line setting. In patients who aren’t progressing and are tolerating it well, more is better. More on this theme in my next post.