Bevacizumab and erlotinib in the treatment of patients with metastatic renal carcinoma (RCC): Update of a phase II multicenter trial

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Abstract
4540 Background: Several new drugs which target signaling pathways downstream from the VHL gene product defects characteristic of clear cell RCC have shown antitumor activity in advanced RCC. We previously reported promising results with a combination of bevacizumab and erlotinib in patients (pts) with metastatic RCC. These drugs target 2 pathways critical to the growth and dissemination of clear cell RCC. We now present updated efficacy data after a median follow-up of 16 months. Methods: Eligibility criteria included: metastatic clear cell RCC, 0 or 1 previous systemic regimens, previous nephrectomy, ECOG PS 0 or 1, adequate organ function, no active CNS metastases, no bleeding abnormalities, informed consent. All pts received bevacizumab 10mg/kg IV q 2 weeks, and erlotinib 150mg po daily. Pts were evaluated for response (RECIST criteria) after 8 weeks; treatment continued until tumor progression. Results: Between 2/03 and 1/04, 63 pts were treated: median age 61 years; male/female, 50/13; ECOG 0/1, 36/27. 43 pts (68%) were previously untreated; the remainder had received IL-2 and/or interferon. 15 of 59 evaluable pts (25%) had objective responses (PR 14, CR 1). 36 pts (61%) had stable disease; however, 13 of these pts (22% of total) had minor objective responses (10–30% decrease by RECIST criteria). The median duration of treatment was 8 months; 26 pts received > 12 months of therapy. Median and 18-month progression-free survival (PFS) are 11 months and 26%, respectively. Median survival has not been reached; 78% and 60% of pts were alive at 12 and 18 months, respectively. 1-year PFS in the subgroups with major response (PR/CR), minor response, and stable disease are 80%, 57%, and 27%, respectively (p=.007). 2 pts discontinued treatment because of grade 3 skin toxicity; only 1 grade 4 toxicity occurred (GI bleed). Grade 3 toxicity: diarrhea 13%; rash 13%; nausea/vomiting 10%; hypertension 8%; bleeding 6%; proteinuria 6%; pruritus 3%. Conclusions: These updated results confirm the high level of activity of bevacizumab/erlotinib in patients with metastatic RCC, and support continued exploration of this combination as well as other rational combinations of targeted agents. No significant financial relationships to disclose.

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