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Dr. Jack West is a medical oncologist and thoracic oncology specialist, and Executive Director of Employer Services at the City of Hope Comprehensive Cancer Center in Duarte, CA.

Avastin in Older Patients: Survival Benefit Not Seen
Tue, 06/12/2007 - 22:45
Author
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

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:

ECOG 4599 schema (click to enlarge)

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):

ECOG efficacy by age ECOG 4599 OS PFS in elderly

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:

ECOG 4599 toxicities by age

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.

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