Abstracts to Watch in Lung Cancer for ASCO 2008 (Part 1)

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May 24, 2008 - 9:24 pm email to a friend printer friendly view / write comments

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Dr. West

   Now that ASCO has changed its policy and has published the vast majority of its abstracts online in the weeks preceding the annual meeting (next week, where most of the biggest developments in clinical cancer research are presented), we can peek at some of these summaries and determine many of the reports that are going to be most important in managing lung cancer.  Here’s a list of ten abstracts that I’ll be covering in more detail after the meeting, where the actual data will be presented, that will be ones worth noting.  I’ll cover five today, and five in the next post.

1) FLEX trial (abstract withheld): The only one that we don’t have an abstract for, because it’s been selected for the plenary session and designated as among the most important at the meeting.  This phase III randomized trial of cisplatin/navelbine alone vs. same chemo with the EGFR inhibitor erbitux (cetuximab)  as first line treatment for advanced NSCLC has already been declared positive for a survival benefit in a press release (see post here) from all the way back in September, 2007, with no additional information since then).  With that news, it already becomes a player.    Where it fits in relative to current standards really depends on the actual numbers.  The lung cancer world will be watching…

2) SWOG 0124 (abstract here): This trial is probably the most important one being presented on the topic of SCLC this year.  As a background, we’ve had years of back and forth about whether the cisplatin/irinotecan combination that has appeared so beneficial in Japan is actually better than our current US standard of platinum/etoposide in a North American population (see discussion of this saga in a prior post here).  The SWOG 0124 trial randomized 671 patients with previously untreated ED-SCLC randomizes patients to cis/irinotecan vs. cis/etoposide to provide that answer.   Sadly, it wasn’t worth the wait: both looked very comparable, with more blood count-related side effects with etoposide, more diarrhea with irinotecan, but overall no meaningful differences in activity.  The hope is that we can use genetic profiles of patients to predict which drugs will work better in which patients.

3) Maintenance alimta after first-line chemo (Lilly JMEN trial, abstract here): I already decribed this trial and the overall results in a recent post, but it’s worth mentioning here because it will likely emerge as one that will change clinical practice.  To recap, non-progressing patients after four cycles of platinum-based chemo were randomized to maintenance alimta or a placebo IV therapy once every three weeks.  There was a very striking statistically significant, and I would argue clinically significant, improvement in progression-free survival, and a survival benefit of more than two months that was right on the cusp of statistical significance.  Combined with a trial last year that showed a similar benefit from maintenance taxotere, these two trials provide a compelling argument in favor of maintenance chemo for patients who don’t demonstrate progression after four cycles of first-line platinum chemo.  But how do we integrate this with maintenance avastin or erbitux, and would we see a similar benefit with tarceva?  All good questions for which we don’t have answers.

4) IGF-1R antibody CP-751,871 in NSCLC (abstract here): The class of drugs that target the insulin-like growth factor-1 receptor (IGF-1R), of which there are several being studied as anticancer agents, have begun to generate some significant interest, as described in a prior post.   A smaller, earlier version of this trial of carboplatin/paclitaxel alone or with this novel agent from Pfizer was presented with 73 patients last year (abstract here), and it generated some interest, particularly with a suggestion that the non-adenocarcinoma patients were doing better with the study drug.  A year later, the investigators have added another 108 patients in this randomized phase II trial, and the results still appear encouraging, especially in the patients with squamous cell NSCLC, in whom there was a 72% response rate with the chemo/IGF-1R antibody approach.  It’s not enough to make it a standard drug, but it certainly shows enough promise to generate enthusiasm for CP-751,871 as it moves into later clinical testing.  We can only hope it’s assigned a catchier name soon.

5) “Randomized Discontinuation” trial with nexavar (abstract here): I’ve previously introduced the multikinase inhibitor and antiangiogenic agent nexavar (sorafenib) as a treatment for lung cancer (prior post here), but its role in lung cancer remains unclear.   This trial fm ECOG (E2501) uses a very novel approach called a “randomized discontinuation” strategy in which previously treated advanced NSCLC patients are given run-in period on nexavar, then checked for response.  Patients with progression are removed, and those with a response stay on it, but the remainder, with stable disease, are randomized to stay on it or switch to a placebo.  This approach provides an opportunity to more carefully test an agent with likely milder beneficial effects in patients with tendency toward more stable results.   Nexavar showed favorable results, and the ECOG lung cancer committee deserves credit for piloting this creative, if somewhat confusing, new trial design.

   I’ll cover additional abstract previews in my next post.  I’ll also have more information to provide on these abstracts I described above after ASCO, likely with each of these meriting its own dedicated post.

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