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INTEREST Trial

Dr West

TITAN Trial: Comparison of Chemo and Tarceva in Patients Who Progressed Early on First Line Chemo for Advanced NSCLC

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One of the trials presented at the Chicago Multidisciplinary Symposium in Thoracic Oncology last month was the TITAN trial, one of a pair of studies conducted in Europe to test the oral EGFR inhibitor Tarceva (erlotinib) in patients with chemotherapy pre-treated advanced NSCLC. The other trial, SATURN, was designed to test Tarceva as a maintenance therapy vs. placebo in patients who had shown a response or stable disease after four cycles of first line chemotherapy (without the VEGF inhibitor Avastin (bevacizumab)) has been summarized previously and ultimately led to the approval of Tarceva as a maintenance therapy in this patient population. But what happened to the significant fraction of patients who progressed by the time of the repeat imaging after four cycles of first line platinum-based doublet chemotherapy? They were directed to the TITAN trial, which was a head to head comparison of Tarceva vs. either Taxotere (docetaxel) or Alimta (pemetrexed), both well studied and commonly used second line agents for advanced NSCLC. The trial looked for an improvement in overall survival with Tarceva.

patient-distribution-on-saturn-vs-titan-trials (click on image to enlarge)

The trial closed earlier than planned, due to slow enrollment, with just 424 patients, which leaves it quite underpowered to detect a difference even if there really is one between the two treatment approach. Still, there may be some conclusions that can be drawn from what they saw, even if limited by smaller numbers than needed to say anything definitive.

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Dr West

Lung Cancer FAQ: My advanced NSCLC has progressed after initial chemo. What are the leading options now?

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In the last decade, the treatment of NSCLC has evolved very significantly, and one of the leading ways has been that we’ve gone from having no established role for treatment after initial, first line therapy to having multiple agents with a proven benefit.

It’s worth clarifying that as maintenance therapy is increasingly being considered as an option after first line therapy, a distinction between this and second line therapy. Maintenance therapy is given to prolong the period before someone who has achieved a response or stable disease on first line treatment demonstrates progression for the first time, while second line therapy is the term more commonly reserved for treatment after someone has demonstrated evidence of progression for the first time after first line therapy.

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Dr West

Molecular Markers from the INTEREST Trial: Chemo and EGFR Inhibitor Therapy Still Remarkably Equivalent

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Oncologists often have their own ideas about how effective or ineffective a targeted therapy like an EGFR tyrosine kinase inhibitor (TKI) (Tarceva (erlotinib) or Iressa (gefitinib)) is compared with standard chemotherapy options. We’ve seen a lot of new information emerge in the field over the last few years, and we now have evidence that patients with an EGFR mutation generally have excellent outcomes with an EGFR TKI, but many physicians believe that patients who don’t have an EGFR mutation don’t get any benefit from this class of agents, or certainly far less than they get with a standard chemo agent.

The INTEREST trial directly compared Iressa with the standard chemo agent Taxotere (docetaxel), which was the first agent proven to improve survival for previously treated patients with advanced NSCLC. As I described in a post when the INTEREST trial was initially reported, this was a worldwide trial of 1466 previously treated patients with advanced NSCLC who were randomized to one treatment or the other, and I previously reported the results showing that Iressa and Taxotere led to an identical survival:

interest-os-curve

(click on image to enlarge)

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Dr West

The INTEREST Trial of Chemo vs. Iressa as Second Line Treatment for Advanced NSCLC

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In a post several months ago, I described the results of a trial from Japan, designated V-15-32, that directly compared Iressa to Taxotere as a second line therapy. Although overall comparable, the study showed that Japanese patients receiving Iressa had a higher response rate, but despite that had a lower median and one year survival. Although Iressa overall has not shown the same degree of clinical benefit as the very similar drug Tarceva, these results were perhaps a bit surprising because EGFR inhibitors have been most effective in Asia, where a higher proportion of lung cancer patients are never-smokers and/or have an EGFR mutation. But the Japanese trial had the problem that more patients randomized to Taxotere received a potentially effective therapy (different agent with potential activity in previously treated patients) after the trial drug than patients on the Iressa arm.

One of the trials presented at the Presidential Symposium at the recent World Conference on Lung Cancer in Seoul, Korea, was called the INTEREST trial (I don’t remember what the acronym stands for, except that it was a major stretch), led in North America by my friend Ed Kim from MD Anderson Cancer Center. This trial (abstract here) had almost the exact same design as the Japanese study, again randomizing previously treated patients to either Iressa 250 mg daily or Taxotere IV every three weeks.

INTEREST schema (Click to enlarge)

The INTEREST trial was run around the world, accruing 1466 patients from 149 centers in 24 countries, making it the largest trial in previously treated patients with NSCLC that has ever been conducted. The Taxotere dose was also 75 mg/m2 every 3 weeks, the FDA-approved standard in the US based on a proven survival benefit in North American trials, while the Japanese V-15-32 trial used 60 mg/m2, which is the standard in Japan and appears to be a dose with the same general toxicity and effectiveness as a higher dose in North American/European populations. Otherwise, the INTEREST trial asked the same question as the Japanese trial but in a broader audience. Specifically, one of the reasons it was so big is that it was looking to see whether the two approaches could be proven to have the SAME survival/clinical benefit, which requires more patients than showing that one is better than another. The trial was also designed to look at whether patients with EGFR gene amplification as measured by the FISH test. Continue reading


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