Article and Video CATEGORIES

Cancer Journey

Search By

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.

Moving Forward with Maintenance Therapy: New Trial Asking Single Agent or Combination?
Tue, 07/28/2009 - 21:22
Please Note: While this is Still Excellent Background Info, New Treatments and Procedures Have Emerged Since this Original Post
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

The question of whether we should routinely have advanced NSCLC patients with a response or stable disease after four cycles of first line chemotherapy transition to immediate maintenance therapy or be watched during a treatment break has been the subject of several clinical trials and debates in the lung cancer community over the past couple of years. But now, with chemotherapy and the EGFR inhibitor tarceva (erlotinib) showing a survival benefit in clinical trials, we may be reaching a tipping point where the question is no longer whether to do maintenance therapy, but rather which agent or agents are the best maintenance therapy strategy. We also need to reconcile the idea of starting a new maintenance therapy with the concept of continuing a treatment from the first line setting. The Eastern Cooperative Oncology Group (ECOG), one of the main networks of cancer centers doing collaborative cancer research together in the US, is moving ahead with a trial that aims to address some of these questions. ECOG is the network that conducted the important clinical trial (called ECOG 4599) that established the combination of carboplatin/taxol (paclitaxel) with avastin (bevacizumab) as a potential pace-setting regimen in the US after it was shown to lead to a significantly longer survival than carbo/taxol alone for patients with non-squamous advanced NSCLC. This approach entails continuing the avastin as a single agent after a fixed number of cycles of avastin with chemotherapy, typically 4-6 cycles (in the absence of progression or prohibitive side effects). At the same time, the trial of maintenance alimta (pemetrexed), previously summarized, showed a very impressive survival benefit from having patients switch to alimta after four cycles of chemo if they hadn't progressed and were doing well.

So with a couple of competing possible standards of care, should we have patients continue with avastin, switch to alimta, or (stop me if you've heard this one...) combine the two together? Yes, this means we're talking about two very pricey medications instead of (just) one, but we've also seen that tarceva significantly improves progression-free survival combined with avastin compared with avastin alone. This shows me that avastin alone isn't necessarily the ceiling of what we can do for patients. In addition, earlier work has shown that the alimta/avastin combination is generally very manageable for patients and looked favorable as a second line regimen, so this is essentially just shifting that a little earlier. The trial, designated ECOG 5508, is being run by my friend Suresh Ramalingam, who is the Director of the Lung Cancer Program at Emory University in Atlanta. It's just getting final approvals and will enroll nearly 1300 patients with previously untreated non-squamous advanced NSCLC to receive carbo/taxol/avastin for up to four cycles. Those who haven't progressed (estimating about 900) will then be randomized equally to one of the three arms: 1) maintenance avastin (just like the older ECOG 4599 trial) 2) maintenance alimta (like the "JMEN" trial of maintenance alimta), or 3) maintenance alimta/avastin (is more better? can avastin improve alimta, and alimta improve avastin?)

E5508 Trial Design

E5508 Trial Design

(click to enlarge)

Note that there isn't an arm here that receives observation or a placebo. We'll see if American oncologists are disinclined to enroll onto this trial because they just don't believe that maintenance therapy is valuable, but I suspect that it will accrue readily. It will be years before this trial is completed and reported, but in the meantime, I think that the range of options being offered here suggests that the shift toward maintenance therapy will continue and that the debate will move from whether to give maintenance therapy to what agent or agents are the best choice for maintenance therapy.

Next Previous link

Previous PostNext Post

Related Content

Forum Discussions

Hi Stan! It's good to see you. I can only imagine what this last year has been like for you and hope the grieving is getting more manageable every day. GRACE...

It is so good to hear from you, and my sentiments are the same as Janine's.  You are definitely why we do this, and we truly appreciate your kind words.  Happiest...

Hi and welcome to GRACE.  I'm sorry mother is experiencing oligoprogrssion.  This often happens when some of the cancer cells acquire a resistance to alecensa's effects.  Those cells can be radiated...

help Mom to continue using Alectinib. Thank you for the video list as well. Is there any experience or some period in which SBRT works, is it individual or are there...

Oh yes! SBRT (Stereotactic body radiation therapy) is a very focused type of radiation that is able to target and kill the tumor without the destruction of healthy tissue. The goal...

Hi again, thank you very much for the detailed response. I hope that SBRT will help my mom and that she will use Alecensa for a long time and after Alecensa...

Hello and welcome to GRACE.  I'm so sorry about your person.  Cancer is a horrible disease.  We can't diagnose or interpret scans here nor should you expect anyone else to make...

Recent Comments

Thank you Stan!
By dbrock on Fri, 12/02/2022 - 14:02
Hi Stan! It's good to see…
By dbrock on Fri, 12/02/2022 - 12:49
thanks for response
By Srdjan Ćurić on Thu, 12/01/2022 - 12:21
Oh yes! SBRT (Stereotactic…
By Srdjan Ćurić on Wed, 11/30/2022 - 11:54