The Midas Touch: Avastin in Platinum-Resistant Ovarian Cancer
| Jun 2, 2012
The winning streak for Avastin continues with successful results reported in pivotal trials for ovarian cancer at 2011 and 2012 ASCO. The AURELIA study was the first randomized study to evaluate the clinical efficacy of Avastin in combination with chemotherapy in platinum-resistant patients. Eligible patients were randomized to receive chemotherapy (paclitaxel, topotecan or liposomal doxorubicin) alone or in combination with Avastin (15 mg/kg). The trial was designed to achieve a HR of 0.7 (anticipated PFS improvement from 4 to 5.7 months) and the results did not disappoint. Avastin plus chemotherapy achieved significant improvement in primary endpoint of median progression-free survival (mPFS= 6.7 months in Avastin plus chemotherapy versus 3.4 months in control arm; HR 0.48, p<0.001). In addition, the ORR was also significantly improved for the Avastin plus chemotherapy arm compared to the chemotherapy alone arm (ORR: 30.9% versus 12.6%; p<0.001). The control performed very comparably to the current standards of care in platinum-resistant patients: paclitaxel, topotecan and liposomal doxorubicin. There were no untoward toxicities reported with Avastin plus chemotherapy arm and most common toxicities included Grade >2 hypertension (20%), proteinuria (10.6%) and thromboembolic events (5%). There were slightly higher reports of peripheral sensory neuropathy and hand-foot syndrome observed in Avastin plus chemotherapy arm but this was attributed to the fact that patients in the combination arm remained on therapy for longer time compared to the chemotherapy alone arm.
With the caveats of cross-trial comparison, Avastin plus chemotherapy does look better than current standards. Unfortunately the authors of the presentation did not provide any of the efficacy results according to each chemotherapy agent used in the study. Disappointingly, no information on the increasingly important secondary endpoint, overall survival, was provided. The overall survival data from AURELIA study are anticipated in 2013 and Roche/Genentech have indicated that they will file for approval in ovarian cancer with the FDA based on the survival results.
Although the trial achieved its primary endpoint, the discussant (Dr. Seiden) was skeptical that Avastin would achieve a survival benefit. Dr. Seiden correlated the PFS data from AURELIA with that observed in the GOG-0218 trial (first-line Avastin plus chemotherapy), which demonstrated a 2.8 month PFS benefit (comparable to 3.3 months observed with AURELIA) but failed to demonstrate a survival benefit. In spite of Dr. Seiden’s skepticism on the survival benefit, the fact is that Avastin did achieve a significant PFS benefit and physicians are willing to accept PFS benefit in ovarian cancer. As mentioned before, Avastin is not yet approved in the United States; however, it does have a category 2A recommendation in the NCCN guidelines. It is preferred in almost one-third of platinum-resistant patients either as a monotherapy or in combination with other agents according to Kantar Health’s CancerMPact Treatment Architecture
U.S. physician survey. The newly reported results from AURELIA are likely to augment further adoption of this combination in the United States; although questions of which is the best combination partner will remain unanswered until further subset analysis are reported. The situation is slightly different in Europe with the EMA already granting Avastin a label in first-line setting. Its indication in Europe will likely be expanded to include platinum-resistant patients and platinum-sensitive patients (based on improving PFS in the previously reported OCEANS trial). Kantar Health’s Treatment Architecture Western Europe physician survey from the first quarter of 2012 reports 10% utilization of Avastin in platinum-sensitive patients and approximately 20% in platinum-resistant patients. Unlike breast cancer, Avastin seems to have been able to demonstrate a consistent and more robust PFS benefit in ovarian cancer; whether this translates into an OS benefit will be revealed in 2013.