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Clinical Trials with Sutent (Sunitinib) in NSCLC

April 4, 2008 - 8:06 pm email to a friend printer friendly view / write comments

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Dr. West

One of the novel agents being studied in lung cancer is sutent (sunitinib), a multi-targeted oral anti-angiogenic drug that I’ve described in a prior post. While I’ve mentioned a small study I’m leading at my own institution with this agent in advanced NSCLC patients with bronchioloalvelar carcinoma (BAC) or who have never smoked (information here), I wanted to describe a couple of larger studies that are being run by Pfizer, the company that is developing sutent, in lung cancer. Their development program is a series called the SUN trials, for Studies to UNderstand Sunitinib, another acronym that is a bit of a stretch in order to be memorable.

These trials are based on the combination of sutent/tarceva, which has been studied in a limited trial in kidney cancer (abstract here), and another one in NSCLC is being conducted at the University of Wisconsin (information here).

The largest trial is SUN-1087, which is an international phase III randomized trial of the combination of sutent and tarceva (erlotinib) compared to a current standard for previously treated patients with advanced NSCLC of tarceva with a placebo. The SUN-1087 trial is ongoing and will plan to enroll 956 patients in the second or third line setting, and it patients with any kind of NSCLC (adenocarcinoma, squamous, or less common subtypes). It will look at potentially important variables such as whether enrolled patients received prior avastin (bevacizumab), whether they are a never-smoker, ex-smoker, or current smoker, and also their EGFR status (I believe my looking at immunohistochemistry, the levels of EGFR protein on tumor cells. These factors will be monitored and compared between the two arms so that neither arm receives far more never-smokers, prior recipients of avastin, etc. – a balancing act called stratification. The tarceva will be given at the standard starting dose of 150 mg daily, with sutent at 37.5 mg daily, and the trial will treat all patients until they develop either progressing cancer or prohibitive toxicity. The goal of the study will be to see whether the tarceva/sutent provides a significant overall survival (OS) advantage over tarceva alone (with tarceva). Further information on this trial, including participating sites, is available here.

A smaller trial known as SUN-1058 has a very similar design of tarceva/sutent vs. tarceva alone, but it doesn’t have a placebo included. It is enrolling essentially the same population of previously treated patients with advanced NSCLC (second and third line), with any NSCLC subtype, but will only enroll a total of 126 patients and will be looking at progression-free survival (PFS) as the primary endpoint. Further information on this trial, including participating sites, is available here.

You might ask yourself why a company would conduct two trials with such similar designs – it’s not a typical approach, and I’m still not sure why the company would do this. However, I speculate that the reason for running a small trial at the same time as a large trial is a strategy to obtain early feedback from a small trial looking at PFS (a quick endpoint) that could potentially lead to changes or an early termination of the larger trial looking at the longer-term endpoint of OS before having invested far more millions into the larger trial.

Several other smaller trials are also being conducted with sutent. One is evaluating the utility of it as a single agent for patients with brain metastases who have received prior radiation (information here). Another tests sutent with either alimta or alimta and cisplatin or carboplatin (information here). Finally, an ambitious one is adding sutent to the triplet of carbo/taxol/avastin (bevacizumab) as an initial therapy for patients with advanced NSCLC (information here).

I’m concerned about potentially punishing side effects of trials that combine sutent with other agents, since it can be challenging enough even as a single agent. But there have been documented responses to sutent even in previously treated NSCLC patients, so it’s certainly worth testing the feasibility and activity of this agent alone and in combinations.

I’ll cover sutent trials in SCLC in a separate post soon.