A press release today informs us that the ATLAS trial of maintenance avastin (bevacizumab) combined with tarceva (erlotinib) vs. avastin with placebo was positive for a significant improvement in progression-free survival (PFS). We had already learned that the very similar SATURN, of maintenance tarceva vs. placebo in patients who weren't on avastin was also positive for an improvement in PFS (see prior post), though we don't have details yet. Here's the design of these two trials: (click to enlarge) What we've learned so far about the ATLAS trial is that an interim planned analysis of safety and efficacy showed that there was a significant improvement in progression-free survival that led to the stopping of the trial and disclosure of these early results of more favorable PFS in the recipients of tarceva combined with avastin. It had already enrolled 1157 patients, which was its goal, and these patients received avastin with any of several different platinum-based chemotherapy doublets (carboplatin/gemcitabine, carboplatin/paclitaxel, carboplatin/docetaxel, cisplatin/vinorelbine, cisplatin/docetaxel or cisplatin/gemcitabine). If patients hadn't progressed after four cycles of this combination, they would be randomized to avastin maintenance with either tarceva or a placebo pill. The results apparently showed no evidence of any unexpected safety problems, which is important both for broadening our experience of different chemo agents with avastin and because patients with therapeutic doses of blood thinners were able to be enrolled, as were patients with more peripheral squamous cancers that were far from the center of the chest (a minority of squamous cancers).

While these preliminary results add more evidence to the concept that earlier second line therapy may be superior to waiting until starting it later, they also suggest that it may be possible to improve on maintenance avastin -- that avastin alone may not be as effective as avastin with another agent that has established clinical benefit. Other trials are also assessing the role of maintenance avastin with chemotherapy. ECOG is just starting a large randomized trial in which patients will all start by receiving four cycles of carbo/taxol (paclitaxel) with avastin, and then non-progressing patients will be randomized to receive maintenance avastin alone, alimta (pemetrexed) alone, or the combination of avastin and alimta. While some may debate whether an improvement in PFS is enough to lead us to transition toward more routine use of maintenance therapy, it appears that more and more clinical trials are shifting beyond asking whether maintenance therapy is appropriate to a bigger question of what the optimal maintenance therapy strategy should be. We'll learn more about these trials when the full data are presented at upcoming oncology meetings.