CALGB 90206: Bevacizumab plus IF improved PFS in metastatic RCC

2009 ASCO Annual Meeting

Compared with interferon monotherapy, bevacizumab plus interferon improved objective response rate and PFS in patients with metastatic renal cell carcinoma, according to data from the CALGB 90206 trial.

“Overall survival is greater in patients with metastatic clear cell RCC receiving bevacizumab plus interferon as initial systemic therapy compared to interferon alone, although this did not meet prespecified defined criteria for significance,” Brian Rini, MD, associate professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Cleveland, said during his presentation at the 2009 ASCO Annual Meeting.

The study included 732 patients with previously untreated metastatic renal cell carcinoma with a clear cell component and Karnofsky performance status ≥70%. Patients were stratified by nephrectomy status and number of MSKCC adverse features. They were then randomly assigned to bevacizumab (Avastin, Genentech) 10 mg/kg IV every two weeks plus interferon 9 million units subcutaneously three times per week (n=369) or interferon monotherapy (n=363). The primary endpoint was OS. Median follow-up was 46.2 months.

Though not statistically significant, OS was greater among patients assigned bevacizumab plus interferon compared with interferon alone: 18.3 months vs. 17.4 months.

PFS was superior among bevacizumab plus interferon compared with monotherapy: 8.4 months vs. 4.9 months (HR=0.71; 95% CI, 0.6-0.8). Overall response rate, complete response and partial response all favored the combination arm. In addition, though not statistically significant, duration of response was longer in patients assigned combination therapy compared with monotherapy: 11.9 months vs. 9.7 months.

Patients assigned combination therapy had greater toxicity compared with patients assigned monotherapy, including fatigue (37% vs. 30%), anorexia (17% vs. 8%), hypertension (11% vs. 0%) and proteinuria (15% vs. <1%).

“As is now well recognized, during the conduct of this trial several other therapies — active VEGF targeted and other therapies — emerged, and therefore the vast majority of patients who were initially entered on the study received subsequent therapy. Approximately 56% overall received at least one subsequent systemic therapy,” Rini said.

Median OS was evaluated according to whether or not patients received subsequent therapy. Patients assigned to the combination arm who received a second-line therapy had improved OS compared with those assigned monotherapy who had at least one second-line therapy: 31.4 months vs. 26.8 months (HR=0.80; P=.055).

In contrast, patients who did not receive second-line therapy had median OS of 13.1 months for the combination arm and 9.1 months for interferon monotherapy. Baseline prognostic factors were more favorable for patients who received second-line therapy. “Thus, these data support that the best overall survival in achieved in patients with favorable underlying disease biology who receive initial bevacizumab plus interferon and subsequently receive other active therapy upon progression” Rini said.

HRs for OS were consistent across groups, demonstrating a maintained benefit from bevacizumab plus interferon regardless of second-line therapy status, though differences in absolute OS across groups were apparent. – by Stacey L. Adams

For more information:

Rini B. #LBA5091. Presented at: 2009 ASCO Annual Meeting; May 29-June 2, 2009; Orlando.