Thursday, 11 February 2016

Avastin alone vs. Avastin & chemo

To those of you battling with recurrent GBM (or grade 3 tumors): Are you being treated with Avastin alone or Avastin plus chemo? 
My wife is being treated with Avastin + lomustine (CCNU). Yet I have just seen that a recently completed phase 3 study concludes that combining Avastin and CCNU does not improve survival. The prior phase 2 study indicated prolonged PFS for MGMT methylated patients receiving the combination, but the 9 months overall survival was precisely the same (67 %) for MGMT methylated patient receiving the combination vs. those receiving Avastin alone.

The obvious question is: Is it worthwhile enduring the extra toxicity events that the chemo causes when it is so questionable if anything is gained by it? 
Would it not be better to stick to Avastin alone (and combine it with DCA, Chloroquine, CBD, and Honokiol, as recommended by Stepehen)?


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  2. Unlike the randomized phase 2 BELOB trial, which included 3 arms (CCNU alone, Avastin alone, and the two combined), this phase 3 trial was comoparing CCNU alone versus CCNU + Avastin. There was no arm treated with Avastin alone.

    An important thing to keep in mind is that the overall results presented here do not break down the data according to MGMT status. I suspect for the patients with MGMT-unmethylated GBMs, Avastin + CCNU would have better outcomes than CCNU alone, given that CCNU is not likely to provide much benefit in this subgroup. However, it's debatable whether CCNU + Avastin is any better than Avastin alone in this subgroup. PFS-6 for the unmethylated MGMT group in the BELOB trial was still best with combination treatment, but the OS breakdown was not given based on MGMT status.

    In the phase 3 trial, the OS benefit of adding Avastin would have been diluted to some extent due to crossover (35.5% of the CCNU arm added Avastin at further progression).

    The BELOB trial showed that adding CCNU to Avastin made a very big difference in terms of improved PFS for the MGMT-methylated subgroup, and I think this decision regarding CCNU should be informed by MGMT status.

    1. this is all very confusing. When the doctor at Dana Farber told us about CCNU + Avastin making no difference then Avastin alone, she never mentioned anything else. She just told us it wasnt worth it the extra toxicity.

    2. It's not worth the extra toxicity, unless you have a tumor type that might respond to CCNU, and this depends to some extent on MGMT status.

      In the randomized phase 2 BELOB trial, which was for first recurrent GBM, 26% of patients with MGMT-methylated GBMs were progression-free at six months with CCNU alone, while 0% of patients with MGMT-unmethylated GBMs were progression-free at 6 months with CCNU alone. A fairly significant difference.

      CCNU is not guaranteed to be helpful even where MGMT status is methylated, but the chances of it being beneficial are higher in those cases.

    3. As Thomas pointed out, in the BELOB trial, 9-month overall survival rate was identical for MGMT methylated GBM in the Avastin alone group and the Avastin + CCNU group. However, single time-point analysis can be deceiving, and we would have to look at survival rate in these groups over time, not just at a single point (in this case 9 months), to get a clear picture.

    4. On the other hand, if I were considering a vaccine or other immunotherapy, I would not compromise that by doing a chemo that is as hard on the immune system as CCNU.

    5. When we were at Dana Farber in Jan 2015 they told us at recurrence would use CCNU and avastin or resection or clinical trial. We sawDr Reardon My sis is partially methylated, IDH1, and has secondary GBM (but was only found when was GBM). They said cause of the results of the BELOB trial BUT this was before the other study.

  3. My mom was diagnoseds with grade 3 Astrocytoma in April 2013 it was inoperable so she went through 35 sessions of Image guided RT 3sessions of cyber knife 6months of Tmz by tumor came more aggressively in just 6months so she was put on an aggressive chemo of Avastin and irinotican for about 1year and whole of 2014 in 2015 she was put on just Avastin which continues to this day as maintenance every 3weeks she shashi completed over 62sessions of CT and disease is considered stable as per last 6 Mri done over 2years, I would strongly strongly strongly suggest giving a high dose of the best absorption circumn you can find everyday believe me I don't know what curcumin does but she is on no meds except Avastin on a maintenance cycle

  4. Hi Karan, Daninha, and Stephen,

    I just want to say thank you very much for your helpful comments. Fantastic with such a supportive community.

    Very best,