As described in one of my first posts, Avastin was approved by the US FDA for the first line treatment of advanced NSCLC in patients with non-squamous cancers, no history of coughing up blood, and no brain metastases, based on the positive trial ECOG 4599 (abstract here) that demonstrated a survival benefit for carbo/taxol/avastin compared with carbo/taxol alone. The trial included only active patients with a good performance status, and we saw that while patients lived longer on average with avastin, they also had increased side effects. This leaves us with some open questions about whether sicker and/or older patients would be well served by the combination of chemo with avastin. This year at ASCO we learned something about the value of avastin in an older population.
A friend of mine, Dr. Suresh Ramalingam from the University of Pittsburgh Medical Center, presented data from the ECOG 4599 broken down by patient age (abstract here). To review, the trial divided about 878 patients between carbo/taxol and carbo/taxol/avastin for up to 6 cycles, and then the patients on the avastin arm received maintenance avastin if they didn’t show progression after 6 cycles of chemo/avastin:
Among 850 patients analyzed (with age available), 26% were 70 or over, which did a better job representing older patients than preceding large cancer cooperative group trials. Although response rates were higher with Avastin for both older and younger patients, survival was better with chemo + avastin for younger patients only (this also meant that the benefit in younger patients was more profound than the impressive benefit for the trial in general):
This analysis also showed that older patients were disproportionately affected by toxicity with avastin compared with younger patients. This table shows the significantly greater side effects seen in elderly patients:
Taken together, these findings are compelling enough for me to likely make different recommendations for many elderly patients, in whom I’d be much less inclined to recommend avastin with chemo. There’s still room to treat patients individually, but I think these results suggest one potentially important way to refine current treatment guidelines.
posted by Dr. West @ 10:45 pm link to this post
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June 13th, 2007 at 9:19 am
What a timely post…we were torn whether to add Avastin to my mom’s next chemo and decided against it. One oncologist recommended it because she didn’t have any of the high risk factors while the other did not, citing the reasons you mention for elderly patients. I feel better now about our decision. Thanks very much!
Betty
June 13th, 2007 at 10:30 am
Will this affect your recomendations regarding Tarceva/Avastin in those over 70?
Jeff
June 13th, 2007 at 11:27 am
I find this timely for myself as well. I like to think ahead one step, so I’ve been researching my options if and when I fail Tarceva therapy. One issue will be monotherapy vs. a different platinum-based doublet than the one I failed on the first round (Carboplatin/docetaxel). I may try to talk my doctor into Cisplatin/Gemzar, as I’m young and still in pretty good shape.
The other issue will be whether to add Avastin to whatever treatment we choose (I didn’t take Avastin in the initial chemotherapy because I was in a Velcade trial). I’m not in a high-risk group for Avastin, but I’m on the border due to some cardiac issues. Considering that this study shows (indirectly) that the survival effect for Avastin is larger than previously thought in younger people, I will argue vigorously for Avastin. We’ll see what my doctor, one Suresh Ramalingam, thinks of this recent work. It’s a small world out there!
June 13th, 2007 at 7:20 pm
I’m glad people find this issue a timely one. We’re certainly learning some of the nuances of avastin as we go. While I do think that many of the principles of chemo +/- avastin apply across several chemo agents/regimens, I think the avastin/tarceva combination may be different enough, as a non-chemo approach, that I would reserve judgment and would not presume that the same trends apply. We will likely have the opportunity to learn more about nuances like age, performance status, and molecular correlates with all of these combinations, including avastin/tarceva, as ongoing trials are completed and analyzed.
Neil, please give Dr. Ramalingam my best when you see him. I’m sure he’ll always give you thoughtful counsel.
-Dr. West
June 26th, 2007 at 8:15 am
I saw Dr. Rama today. He says hi. He also reported that my scans were stable (two enlarged lymph nodes in mediastinum, one in supraclavicualar area, all the same size as two months ago). No new growth, no tumor per se.
Easy call to stay on Tarceva for two more months, but your post on stable disease saved your colleague a couple of minutes of explaining why stable was OK.
June 26th, 2007 at 9:10 am
Thanks for bringing this up. I hope there’s no question about why OncTalk should be very helpful to patients and family members, but it’s not as clear how or whether it might help other physicians. I think to corroborate what they’re recommending it should be a great reassurance, as well as to fill in blanks for the questions that didn’t get covered, either because they weren’t thought of at the time of the appointment or because sometimes the time can be scarce.
Of course, some oncologists will have recommendations that differ notably from what I write here. That’s fine, because I do emphasize that there is plenty of room for different styles, as long as they can express their rationale and it makes sense. On the other hand, if someone isn’t using Avastin in an appropriate patient because they don’t know it’s approved for lung cancer, that’s a problem.
So thanks, Neil, I hoped there were ways that this site could be helpful to and not just “challenge” the oncologists that members here are working with.
-Dr. West