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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.

An Uplifting Case: Tarceva after Iressa Led to a Great Response
Wed, 11/11/2009 - 18:44
Author
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

I just wanted to tell people about a remarkable patient I just saw who is delighted to have had a remarkable response to Tarceva a few years after responding to Iressa. She made my day.

In truth, her case was remarkably long before this. She was diagnosed with bronchioloalveolar carcinoma (BAC) all the way back in 1995 (I was finishing med school, no kids -- life was simpler then). She had undergone a left lower lobectomy for localized disease initially, but her cancer recurred in late 1998, confirmed on a bronchoscopy, and she began experiencing a cough then. She was initially treated with chemo and responded well for several years, with some changes in her chemo but generally doing well before being started on Iressa.

She recalls that within days of starting Iressa, her recurring cough improved dramatically, and she did well on it for over 5 years before her scans progressed and her cough worsened. She ultimately discontinued it back in May of this year, starting Alimta then. And though we might have hoped and expected that she'd show another great response, she actually continued to progress on that, with a worse scan and cough after two cycles. So this shows us that her cancer doesn't quite respond to everything.

All of this treatment was actually by another physician at a different institution, and it wasn't until July of this year that she came over to see me to pursue some clinical trial options not otherwise available to her. She wanted to start on the trial of Sutent (sunitinib) for BAC, which may be closing in the coming months, so she did that. Despite briefly feeling better with less cough, her scans looked a little worse again six weeks later, and she came off of that trial.

We considered various options, and the leading one that seemed appealing was a clinical trial of the investigational agent XL-184, an inhibitor of c-MET and VEGF, combined with Tarceva, since XL-184 is hoped to potentially reverse one of the mechanisms of acquired resistance after a nice response to an oral EGFR inhibitor. However, she couldn't enroll on the trial because she hadn't yet received Tarceva.

In fact, trying Tarceva was another option to consider, since there are a few reports out in the world of people who have responded on Tarceva after progressing on Iressa. It wasn't her leading choice when I first met her, but now it became a reasonable option and a means of enrolling on the next trial if she progressed.

But she didn't progress. Instead, she felt a dramatic improvement in her cough within days, and when I saw her a few weeks ago, I became quite hopeful that she was having a nice response to Tarceva despite her prior treatment with Tarceva. However, since she had also felt a transient improvement in her cough on Sutent but then showed progression, I didn't want to presume anything. But her response was terrific, as you can see below from scan cuts in two different levels:

jl-pre-and-post-tarceva

That's pretty gratifying, and she's thrilled. We don't know how long this response will last, but we'd love to see another one in the range of years.

But what does this mean more generally? In the US, there are very few people out there who have had a great response on Iressa, now off the market for 5 years, but haven't been on Tarceva. If I see another, I'll definitely give them a trial of it. But the bigger question is whether people in Asia and perhaps Europe, where Iressa is now approved for patients with an identified EGFR mutation, will have the opportunity to receive Tarceva after developing acquired resistance to a Iressa.

Unfortunately, I strongly doubt that almost anyone with progression on Tarceva will then respond to Iressa. The standard dose of Tarceva has a stronger biological effect that is otherwise very similar to the standard dose of Iressa, so I think that it's far more plausible to squeeze some more benefit from the stronger medication only. This also raises the question of whether patients who progress on standard or reduced doses of Tarceva could then get more benefit from a higher dose. I haven't seen much to suggest that, but I suppose that someone who progressed on 50 or 100 mg of Tarceva could potentially have the same kind of response we saw here if they received a higher dose. On the other hand, I don't believe that there's any good evidence to suggest that just adding more beyond the standard dose of Tarceva provides additional benefit, at least not in people who aren't current smokers -- there is some limited evidence that there could be a benefit to dose escalation of Tarceva in current smokers.

I don't know how long this will last for her, and unfortunately I think this kind of response is quite uncommon, but it was impressive enough that it was worth talking about! It made my day.

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