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Bevacizumab combination safe, effective for endometrial cancer
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The addition of postoperative bevacizumab to chemotherapy and pelvic intensity-modulated radiotherapy induced high survival rates in patients with high-risk endometrial cancer, according to prospective study results. The regimen also appeared well tolerated.
“This prospective phase 2 trial demonstrated that using pelvic IMRT concurrently with bevacizumab and cisplatin is feasible and has low rates of bevacizumab-specific toxicities,” Akila N. Viswanathan, MD, MPH, senior physician and director of gynecologic radiation oncology at Dana-Farber Cancer Institute and an associate professor of radiation oncology at Harvard Medical School, told HemOnc Today.
Akila N. Viswanathan
Findings from previous studies suggested that bevacizumab (Avastin, Genentech), an antiangiogenic agent, may further reduce the risk for distant metastases when combined with radiation therapy and chemotherapy in patients with high-risk endometrial cancer, according to study background.
Viswanathan and colleagues, thus, sought to assess the rate for grade 3 or worse nonhematologic adverse events within 90 days — which served as the study’s primary endpoint — associated with the combination of bevacizumab, cisplatin and pelvic IMRT followed by adjuvant carboplatin and paclitaxel in patients with high-risk endometrial cancer.
Secondary endpoints included evaluating high-grade adverse events within 1 year of treatment initiation, all treatment-related adverse events, DFS, OS, and local, regional and distant failure.
The analysis included 30 patients who had undergone a hysterectomy and lymph node removal and had multiple high-risk factors.
Patients underwent pelvic IMRT and cisplatin concurrently on days 1 and 29 and received a 5-mg/kg dose of bevacizumab on days 1, 15 and 29 of radiation. Patients then received adjuvant carboplatin and paclitaxel for four cycles.
Seven patients (23.3%; 95% CI, 10.6-36) experienced grade 3 or worse treatment-related nonhematologic toxicities within 90 days of treatment initiation. An additional six patients (20%) developed high-grade treatment-related toxicities between 90 days and 1 year.
“IMRT resulted in few gastrointestinal side effects,” Viswanathan said. “Whether IMRT decreases gastrointestinal complications for all postoperative patients with endometrial and cervical cancer treated with pelvic IMRT compared to 3-D conformal radiation is a hypothesis that is currently being tested in the randomized trial NRG/RTOG 1203.”
After a median follow-up of 25.9 months (range, 13.6-43.4), four patients died, all of whom died of endometrial cancer, and six patients developed recurrent disease. The estimated rate for 2-year OS was 96.7% (95% CI, 78.6-99.5) and 2-year DFS was 79.1% (95% CI, 59.2-90.1).
The 2-year cumulative incidence for regional failure was 7.2% and the cumulative incidence of distant failure was 17%.
Researchers noted that no patients developed pelvic failure within the targeted radiation field and no patients with International Federation of Gynecology and Obstetrics stage I to stage IIIA disease developed recurrence.
“The results of the current study are unique in the finding that bevacizumab may be administered during radiation to the postoperative pelvis without increasing the rate of pelvic complications,” the researchers wrote. “[This regimen] is feasible, has low rates of bevacizumab-specific toxicities and has a high survival rate at 2 years. Future randomized trials should further address the use of bevacizumab in patients with endometrial cancer.” – by Anthony SanFilippo
For more information:
Akila N. Viswanathan, MD, MPH, can be reached at the Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215; email: aviswanathan@lroc.harvard.edu.
Disclosure: One researcher reported an advisory role for Genentech. The other researchers reported no relevant financial disclosures.
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Maurie Markman, MD
In this interesting small (n = 34) phase 2 study involving women with high-risk endometrial cancer, the addition of bevacizumab to cisplatin when administered concurrently with postoperative intensity-modulated radiation, followed by carboplatin/paclitaxel, resulted in relatively high 2-year DFS (79%) and OS (97%) rates. Although these results are provocative and even encouraging, it must be remembered that this was a carefully selected patient population due to concerns for possible excessive treatment-related side effects, and the overall sample size was modest. However, these data certainly support the subsequent conduct of a randomized phase 3 trial to determine if this aggressive approach to primary disease management in high-risk endometrial cancer can improve survival outcomes.
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