Quick Highlights from ASCO 2013 in Lung Cancer: How to Best

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Quick Highlights from ASCO 2013 in Lung Cancer: How to Best Use Our Current Tools

June 9th, 2013 - by Dr. Jack West

http://expertblog.lungevity.org/2013/06 ... ent-tools/

I’m just catching up on sleep after ASCO 2013, so now is the time for me to provide a quick mention of some of the key themes and what we’ll be talking about more in upcoming videos, webinars, and posts.

The first topic we covered in the recent video from ASCO was “Biomarkers France”, an effort in which a network of centers in France that managed to test 10,000 patients, essentially all of the patients with advanced non-squamous NSCLC, for both the most readily actionable mutations like EGFR and ALK, as well as several that may emerge as actionable in the next few years. This work confirms that it’s possible to do molecular marker testing for lung cancer on a national scale, not just at a few academic centers while excluding patients who are community-based. There was also some work on “multiplex” testing (testing for multiple molecular markers at the same time from one biopsy sample) that should lead us all to expect that it will only get easier to do this testing on many people for all of the relevant markers pretty much now, and certainly more in the very near future. Finally, there was even an encouraging trial, called CUSTOM, looking at the feasibility of doing molecular marker testing on small cell lung cancer and thymic carcinomas, so we may see more molecular marker-based trials and treatments emerging for other less well studied thoracic cancers in the near future as well.

There were a couple of high profile tests of various potential molecular markers proposed to help guide selection of an optimal chemotherapy: markers like ERCC1 (suggested to correlate with resistance to platinum-based chemotherapy), RRM1 (potentially correlated with resistance to gemcitabine), and a couple of others that have sometimes even been used to select chemo regimens outside of a protocol (though most experts have advised against this). One was the MADeIT (Molecularly Adapted Design of Individualized Therapy) trial, run largely out of Moffitt Cancer Center in Tampa, and the other was done by the Spanish Lung Cancer Group, out of Barcelona. Both of the studies were stone cold negative, no benefit at all to trying to select a better chemo based on these tests, which turned out to be not very reliable in their readout, which was a known concern about them. These completely negative results, though disappointing, should remind us that tests promising tailored treatment recommendations for chemo, as advertised by several outside labs marketing to consumers, don’t have actual evidence that they help patients do any better.

There were a few studies of maintenance therapy for advanced NSCLC. One, called PRONOUNCE, tested carboplatin/Taxol/Avastin first line followed by Avastin maintenance vs. carbo/Alimta first line therapy followed by Alimta maintenance therapy and showed no significant differences in either efficacy or side effects. Though disappointing, it does show that you don’t need Avastin to do well — you could do just as well with a doublet and no Avastin.

A second maintenance therapy trial called AVAPERL gave all patients first line cisplatin/Alimta/Avastin and then randomized them to maintenance Avastin alone or Alimta/Avastin. After previously showing a significant improvement in progression-free survival (PFS) favoring the combination maintenance therapy arm, an update showed that there was a 4 month better overall survival (OS) in patients on the Alimta/Avastin combination. It seems the Alimta clearly adds to Avastin, but it’s not clear the Avastin adds to Alimta.

There was also a trial called DELTA, done out of Japan, that tested second line Tarceva (erlotinib) vs. standard chemo with Taxotere (docetaxel). It showed a superior PFS for the recipients of Taxotere overall (most patients didn’t have an EGFR mutation), though there was no significant difference in OS. Still, what I think was most notable was that, in the wake of the TAILOR trial presented a year ago that showed a better PFS and also response rate with Taxotere vs. Tarceva in EGFR wild type patients (no EGFR mutation), was that we now have corroborating evidence that in the absence of an EGFR mutation, chemotherapy appears to be a marginally better choice for second line therapy.

One heavily anticipated trial is called PROSE and tested a serum-based approach called Veristrat for its predictive value in determining whether Tarceva is likely to be helpful for previously treated patients with advanced NSCLC. The study prospectively looked at patients randomized to receive second line Tarceva or Taxotere and showed that being found to have a “Veristrat Poor” profile (seen in about 1/3 of patients) was associated with doing far worse when patients were given Tarceva, but these patients did the same as the 2/3 of patients who were “Veristrat Good” when they received chemotherapy. In other words, the Veristrat test was predictive of utility only of EGFR-based treatment, not just predictive of a patient doing well or poorly no matter what treatment they received. The problem, however, is that if you have already decided that second line chemo is a better choice for patients with EGFR wild type based on the findings of the TAILOR and DELTA trials, it’s not clear that you gain anything by doing Veristrat testing. Perhaps you use it to decide whether to try Tarceva as third line therapy or never bother with it at all, but it’s an FDA approved therapy, so I think many patients won’t be looking for a trial that can only tell them that they lose one option that they might have been hopeful about.

I’ll continue with discussion of the key findings for several novel agents in my next summary post.