About a week ago, as most of you are now aware, the annual American Society of Clinical Oncology (ASCO) meeting was held in Orlando, Florida. Tens of thousands of oncologists, nurses, radiation oncologists, pulmonologists, surgeons, radiologists, pathologists, financial advisors, and pharmaceutical representatives descended on Mickey Mouse-land for schmoozing and sunshine… I mean, for the presentation of the most up to date research in the cancer world. Certainly from the standpoint of lung cancer, the most relevant and potentially standard-of-care changing presentations related to maintenance therapy. This has been extensively discussed on this site in the past, but for the newbies this means giving immediate therapy (chemotherapy or targeted drugs) after patients with advanced NSCLC have completed first-line chemotherapyand show no signs of progression. In the past, patients typically would stop all treatment and observe the cancer for signs of progression prior to starting a new treatment, called “second-line” treatment. However, at least 4 major trials in the last few years have tested whether patients would benefit from NOT stopping, but instead moving right on to the second-line agents immediately, before the cancer recurs. The trial of maintenance Alimta (pemetrexed) has already been covered by Dr. Pinder earlier this week. For this post I will cover the first of 2 major phase III trials that tested the concept of maintenance Tarceva (erlotinib), the so-called SATURN (Sequential Tarceva in Unresectable NSCLC) trial. For this trial, nearly 2000 patients with advanced/metastatic NSCLC were given platinum doublet chemotherapy for 4 cycles. After completing 4 cycles, 889 patients who had not progressed were randomized to either single agent Tarceva or to placebo. The primary goal of the trial was to show that maintenance Tarceva improved progression-free survival (PFS).

SATURN Trial Study Design

(Click on figure to enlarge)

A press release earlier in 2009 indicated that the trial had met its endpoint, but this was the first glimpse at the numbers. What they found was that the patients who received immediate Tarceva did have a statistically significantly prolonged PFS, with an improvement of median PFS from 11.1 weeks with placebo to 12.3 weeks with Tarceva.

SATURN Trial Progression-Free Survival (all pts)

The subgroup analysis showed that this slight but significant improvement of PFS held true for just about everyone: men and women, smokers and non-smokers, Asians and non-Asians, and both adenocarcinoma and squamous cell carcinoma. This benefit across all groups is a very important point! From the recent IPASS trial results, we learned that much of the PFS benefit to FIRST-LINE EGFR therapy seemed to be in patients with EGFR mutations. But there did seem to be benefit in patients without EGFR mutations here.

SATURN PFS (Pts w/no EGFR Mutation)

SATURN PFS (Pts with EGFR mutations)

As you can see above, the EGFR mutants (about 10% of patients) had a huge improvement in PFS, while the improvement in wild-type (non-mutant) patients was still statistically significant but much smaller. So one obvious question that comes to mind is this: how clinically significant is a 1 week prolongation of PFS? Well, it depends. For one thing, the overall survival results have not yet been released, which is much more important than PFS. For another thing, the “median” is a research tool and does not adequately describe the true benefit of the patients who are getting Tarceva. To see that, just looking at the top curve is a better judge. The curves stay separate for a year or more, which indicates that some patients really may be benefitting from this treatment for extended periods of time. But when you look at the EGFR mutant versus EGFR wild-type curves below it, what does that tell us? Well, the PFS benefit in the majority of patients certainly seems to be less and not to last as long compared to the mutants. And don’t forget that these patients COULD be recovering from their first-line chemotherapy and going on vacation rather than taking a new drug, with side effects, and coming into the oncologist’s office month after month. Nothing in life is truly free… So should we be offering maintenance Tarceva to all patients, since the benefit seems to carry through to everyone (although some are less equal than others)? You will have to wait and read “Maintenance Tarceva: Ready for Prime Time? Part II: the ATLAS trial” several days from now to see my conclusion. But feel free to draw your own in the meantime, leaving your comments below…