ROCKVILLE, Maryland-For the first time, the US Food and Drug Administration (FDA) has granted a new oncologic drug product approval for indications for two different cancers simultaneously. The agency approved Sutent (sunitinib, Pfizer) for the treatment of patients with gastrointestinal stromal tumors (GIST) whose disease has progressed on imatinib (Gleevec) or who are unable to tolerate imatinib. It also granted Sutent accelerated approval for treating advanced renal cell carcinoma (RCC).
Sutent is an oral multikinase inhibitor that inhibits several receptor tyrosine kinases, some of which, studies indicate, play a role in tumor growth, pathologic angiogenesis, and metastatic progression.
FDA acted based on two key findings submitted by Pfizer. An interim trial analysis showed that GIST patients treated with Sutent had a significant delay in the growth of their tumors and the appearance of new ones, compared with patients who did not get the drug. Data from a Sutent RCC study showed that patients with metastatic kidney cancer whose tumors had progressed following cytokine-based therapy had a response rate ranging from 26% to 37%. The accelerated approval granted to Sutent for RCC, however, was based on partial response rates and duration of responses. Thus, as a condition of accelerated approval, Pfizer must carry out postapproval trials to confirm the drug's benefit in patients with advanced kidney cancer.
"Today's approval of this drug for these indications provides compelling evidence that the use of alternative data endpoints allows us to see the benefits of novel therapies earlier in patients," said Richard Pazdur, MD, director of FDA's Office of Oncology Drug Products.
GIST and RCC Studies
Pfizer submitted two studies, designated A and B, to FDA to support its application for the use of Sutent in treating GIST patients. Study A was an international, randomized, double-blind, placebo-controlled trial involving 312 GIST patients whose disease had progressed during imatinib treatment or who were intolerant to imatinib. As reported at the 2006 ASCO GI Cancers Symposium (see page 26), a planned interim analysis after 149 events had occurred found a significant advantage for Sutent in time to progression (median 27.3 weeks vs 6.4 weeks for placebo; P < .0001), and progression-free survival (median 24.1 weeks vs 6 weeks for placebo; P < .0001). In study B, an open-label, multicenter, single-arm, dose-escalation study, 55 imatinib resistant or intolerant GIST patients received Sutent 50 mg/d on the same 4-week-on/2-week-off schedule as used in the phase III study: 5 (9.1%) had a partial response.
Pfizer presented two single-arm, multicenter clinical studies, designated 1 and 2, in support of Sutent for the treatment of metastatic RCC in patients who had failed prior cytokine-based therapy.
Study 1 enrolled 106 patients and Study 2 accrued 63 participants. In both studies, patients received 50 mg daily of Sutent on a 4-week-on/2-week-off schedule, and therapy continued until patients met withdrawal criteria or their disease progressed; 97% of the patients in the two studies had undergone nephrectomy.
In Study 1, 27 patients (25.5%) achieved a partial response, as assessed by a core radiology laboratory; Study 2 reported 23 partial responses (36.5%) based on assessments by investigators. The median duration of response was 54 weeks in Study 2 and has not been reached in Study 1.
Sutent was well tolerated in both GIST and RCC. The most commonly reported Sutent-related side effects included diarrhea, skin discoloration, mucositis/stomatitis, asthenia, altered taste, fatigue, hypertension, bleeding, and edema.