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The addition of the targeted drug Avastin® (bevacizumab) to chemotherapy may improve outcomes among women with newly diagnosed or recurrent ovarian cancer.1-3

Avastin is a targeted therapy that blocks a protein known as VEGF. VEGF plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Avastin has been approved for the treatment of selected patients with breast cancer, lung cancer, colorectal cancer, kidney cancer, or glioblastoma.

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Recurrent Ovarian Cancer

Results from two Phase III clinical trials suggest that the addition of the targeted therapy Avastin® to chemotherapy delays the progression of advanced ovarian cancer but may not improve overall survival. These results were published in the New England Journal of Medicine.

The role of Avastin in ovarian cancer was evaluated in two Phase III clinical trials that were recently published in the New England Journal of Medicine. The first study enrolled 1873 women with newly diagnosed Stage III or Stage IV ovarian cancer.4 After surgery, women were assigned to one of three treatment groups: 

  • Chemotherapy alone
  • Chemotherapy plus Avastin

Chemotherapy plus Avastin followed by up to 10 months of additional treatment with Avastin alone.

  • Avastin delayed cancer progression: survival without cancer progression was 10.3 months among women treated with chemotherapy alone, 11.2 months among women treated with chemotherapy and Avastin, and 14.1 months among women treated with chemotherapy and Avastin followed by additional Avastin.
  • Overall survival was similar in the three study groups.
  • Side effects that were more common in the Avastin groups included high-blood pressure that required treatment and gastrointestinal perforation.

In a second study, researchers evaluated Avastin among 1,528 women with high-risk or advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer.5 Study participants were treated with chemotherapy with or without Avastin. Women in the Avastin group continued Avastin treatment after chemotherapy was completed.

  • The addition of Avastin delayed cancer progression: survival without cancer progression was 21.8 months among women treated with Avastin and chemotherapy, compared with 20.3 months among women treated with chemotherapy alone.
  • The benefit of Avastin appeared to be greater for the subset of women at high risk of progression.
  • Final information about overall survival is not yet available.

Taken together, these two studies suggest that Avastin given during chemotherapy and for several months afterwards delays the progression of ovarian cancer compared with chemotherapy alone. Avastin increases side effects, however, and may not improve overall survival. Additional research may clarify whether certain subgroups of ovarian cancer patients are more likely than others to benefit from Avastin.

Another Phase III clinical trial (the OCEANS study) evaluated 484 patients with platinum-sensitive disease.1 Study participants were treated with chemotherapy (carboplatin and gemcitabine) in combination with either Avastin or a placebo. After chemotherapy was completed, patients continued to receive Avastin or a placebo until cancer progression.

  • Avastin delayed cancer progression. Progression-free survival was 12.4 months in the Avastin group and 8.4 months in the group that received chemotherapy alone.
  • Response rate was also improved with Avastin: tumor shrinkage occurred in 79% of women in the Avastin group and 57% of women treated with chemotherapy alone.
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In a prepared statement, the lead author of the study noted “The data from OCEANS demonstrate a clear response from [Avastin] in these cancers. These are very meaningful results for patients for whom there are currently limited treatment options available.”

The Phase III ICON7 study enrolled 1,528 women with high-risk or advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. Study participants were treated with chemotherapy with or without Avastin. Women in the Avastin group continued Avastin treatment after chemotherapy was completed.

  • Overall, the Avastin group had a 15% reduction in risk of death (178 deaths in the Avastin group versus 200 in the chemotherapy-alone group).  This difference between study groups did not meet the criteria for statistical significance, suggesting that it could have occurred by chance alone.
  • In the subgroup of women at highest risk of recurrence, Avastin reduced the risk of death by 36% (79 deaths in the Avastin group versus 109 in the chemotherapy-alone group). This result was statistically significant, which suggests that it’s unlikely to have occurred by chance alone.

Platinum Resistant Recurrent Ovarian Cancer

The addition of Avastin®  to standard chemotherapy significantly improved progression-free survival and objective response rates among women with platinum-resistant recurrent ovarian cancer.

The AURELIA clinical trial was a randomized phase III study that included 361 patients with epithelial ovarian, fallopian tube or primary peritoneal cancer—all of whom had disease progression within six months of their last dose of platinum therapy. Patients were randomly assigned to receive Avastin plus chemotherapy or chemotherapy alone. Chemotherapy consisted of one of three standard chemotherapy drugs typically offered in platinum-resistant cancer (paclitaxel, topotecan, or liposomal pegylated doxorubicin. Patients continued to receive therapy until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent Avastin was permitted after progression with chemotherapy alone.

The primary endpoint was progression-free survival (PFS) by RECIST (response evaluation criteria in solid tumors). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes.

Median progression-free survival was 6.7 months in the Avastin/chemotherapy group and 3.4 months in the chemotherapy-alone group. The objective response rate on RECIST criteria was 27 percent in the Avastin/chemotherapy group and 12 percent in the chemotherapy-alone group.

At the time of data cutoff for the final overall survival analysis, 40 percent of patients in the chemotherapy-alone group had crossed over to receive single-agent Avastin after progression. Median overall survival was 16.6 months in the Avastin/chemotherapy group and 13.3 months in the chemotherapy-alone group and this was not considered a statistically significant difference.

Hypertension and proteinuria were more common with Avastin. GI perforation occurred in 2.2 percent of Avastin-treated patients.

Severe bleeding:

  • Treatment with Avastin can result in serious or fatal bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds and vaginal bleeding. These events occurred up to five times more often in people who received Avastin compared to patients who received only chemotherapy.
  • Across cancer types, 0.4% to 6.9% of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin. Treatment with Avastin should be permanently stopped if serious bleeding occurs.7

The researchers concluded that the addition of Avastin to standard chemotherapy significantly improved progression-free survival and objective response rates in women with platinum-resistant recurrent ovarian cancer.6

References:

  1. Aghajanian C, Finkler NJ, Rutherford T et al. OCEANS: A randomized, doubled-blinded, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC). Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA5007.
  2. Kristensen G, Perren T, Qian W et al. Result of interim analysis of overall survival in the GCIG ICON7 phase III randomised trial of bevacizumab in women with newly diagnosed ovarian cancer. Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA5006.
  3. Wright JD, Secord AA, Numnum TM, et al. A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer. International Journal of Gynecological Cancer [early online publication]. July 21, 2007.
  4. Burger RA, Brady MF, Bookman MA et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. New EnglandJournal of Medicine. 2011;365:2473-83.

  5. Perren TJ, Swart AM, Pfisterer J et al. A phase 3 trial of bevacizumab in ovarian cancer. New EnglandJournal of Medicine. 2011;365:2484-96.

  6. Pujade-Lauraine E, Hilpert F, Weber B, et al: Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial. Journal of Clinical Oncology. Published early online March 17, 2014. doi: 10.1200/JCO.2013.51.4489.

  7. Genetech. (2016.) FDA Approves Genetech’s Avastin® (Bevacizumab) Plus Chemotherapy for a Specific Type of Advanced Ovarian Cancer. [Press release.] Can be retrieved from FDA Approves Genentech’s Avastin® (Bevacizumab) Plus Chemotherapy for a Specific Type of Advanced Ovarian Cancer.