You have to keep a score card on what the platinum-free interval is. If the disease recurs in less than 6 months, then the patient can get bevacizumab on label second and third line.
—Bradley J. Monk, MD, FACS, FACOG
We know our ladies with advanced ovarian cancer are going to have multiple recurrences. At one time in their treatment arsenal, they will be receiving it [bevacizumab].
—Paula J. Anastasia, RN, MN, AOCN®
Tough initial treatment decisions have “long-lasting ramifications and affect the entire treatment paradigm” for women with ovarian cancer, according to Bradley J. Monk, MD, FACS, FACOG, of the University of Arizona Cancer Center, Phoenix. In a true collaborative presentation at the Annual JADPRO (Journal of the Advanced Practitioner in Oncology) Live at APSHO (Advanced Practitioner Society for Hematology and Oncology) conference, Dr. Monk joined Paula J. Anastasia, RN, MN, AOCN®, of Cedars-Sinai Medical Center in Los Angeles, to discuss the rationale behind front-line treatment decisions in advanced ovarian cancer, address quality-of-life concerns, and emphasize the importance of genetic testing.1
One size most definitely does not fit all when it comes to initial treatment options for women with advanced ovarian cancer. Among the array of therapies are surgical resection, neoadjuvant chemotherapy, weekly chemotherapy, intraperitoneal chemotherapy, and consideration of targeted therapies. Deciding which one is right for which patient in which order is certainly a challenge that requires the performance of personalized medicine, agreed Dr. Monk and Ms. Anastasia. Further complicating the clinical picture are the array of cell types of ovarian cancer and the diverse molecular abnormalities found in these tumors (such as KRAS mutations in mucinous tumors and BRCA1/2 deficiencies in high-grade serous tumors).
Turning first to surgery for newly diagnosed advanced ovarian cancer, Dr. Monk explained: “The goal of primary surgery is complete resection; if you don’t resect all the cancer, it really doesn’t have any benefit.”
In some cases, he added, the best choice may be neoadjuvant chemotherapy and interval debulking after three cycles of chemotherapy, with supportive data coming from the CHORUS trial.2,3 According to Dr. Monk, “neoadjuvant chemotherapy in these patients who are full of cancer has at least as good of an outcome [as primary surgery followed by chemotherapy] and may be a little better.” He continued: “After three cycles of chemotherapy, the surgery is easier and less morbid. This is done at least half of the time for advanced ovarian cancer patients.”
Ms. Anastasia emphasized the importance of guiding patients through a discussion of the different treatment strategies. She mentioned her preference for taking these conversations a step at a time and not bombarding a newly diagnosed patient with a host of complicated decisions. For her, the tone of these talks centers on survival, hope, and realistic goals. “There is a high probability of achieving a remission, not a cure, with optimal surgical debulking, and with chemotherapy,” remarked Ms. Anastasia.
The presenters turned briefly to the use of weekly chemotherapy, citing supportive data from the JGOG 3016 trial of dose-dense weekly paclitaxel with carboplatin.4 Although Dr. Monk said this treatment improved progression-free survival with the possibility of a survival advantage, he acknowledged its hematologic toxicity profile. Ms. Anastasia agreed, noting several related patient concerns: the inconvenience of weekly treatment, the dose-limiting side effects of anemia and fatigue with the possibility of blood transfusions, and psychosocial issues such as decreased energy for intimacy and sexuality.
What of Intraperitoneal Chemotherapy?
Much attention has been focused on the use of intraperitoneal chemotherapy for advanced ovarian cancer, with a recent long-term update showing its advantage over intravenous chemotherapy extending beyond 10 years.5 According to Dr. Monk, intraperitoneal chemotherapy is not a good choice for those with inadequate surgical resection, but best used for patients who have been debulked to < 1 cm of disease.
As intraperitoneal chemotherapy is a highly toxic and time-consuming regimen, Ms. Anastasia mentioned that quality-of-life issues are key. She added: “Studies show that only 42% of women were able to complete this therapy. It is right for some people, but they have to be optimally debulked.”
One of the most promising targets in clinical trials for advanced ovarian cancer is angiogenesis, declared Dr. Monk. Although adding bevacizumab (Avastin) to the front-line setting is controversial in the United States, it has been approved in Europe, with the supporting clinical data from the GOG 218 and ICON-7 trials.6,7 Dr. Monk commented on the findings of GOG 218, which included bevacizumab in combination with carboplatin and paclitaxel: “There was a progression-free survival advantage in patients who had a lot of disease but not a big enough advantage in overall survival to lead to regulatory approval.”
Ms. Anastasia revealed that she does not use bevacizumab off label in the front-line setting. “One of the reasons that we don’t,” she explained, “is we know our ladies with advanced ovarian cancer are going to have multiple recurrences. At one time in their treatment arsenal, they will be receiving it.” Dr. Monk concurred: “I would argue that every patient probably needs to get bevacizumab at some point.”
For recurrent ovarian cancer, treatment considerations include the platinum-free interval, existing toxicities from first-line treatment, the volume of disease at the time of relapse, and serologic relapse (CA-125 measurement). In addition to participating in a clinical trial and re-treating with a platinum, integrating targeted therapies should be considered. For those with platinum-refractory or -resistant disease, defined as progression during or within 6 months of last chemotherapy, nonplatinum single-agent therapy with or without bevacizumab is indicated. For those with platinum-sensitive disease or recurrence beyond 6 months, a platinum based doublet with or without bevacizumab is indicated.
Dr. Monk added: “You have to keep a score card on what the platinum-free interval is. If the disease recurs in less than 6 months, then the patient can get bevacizumab on label second and third line.”
Monotherapy with the PARP inhibitor olaparib (Lynparza) in advanced ovarian cancer with a BRCA mutation has been approved by the U.S. Food and Drug Administration for deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer after three or more lines of chemotherapy. According to Dr. Monk, “every patient needs to be BRCA tested and have the opportunity to get olaparib.” “It is imperative now that all women with high-grade serous epithelial cancer should have genetic testing,” stated Ms. Anastasia.
“Palliation of symptom management is very important from day 1,” declared Dr. Monk. Ms. Anastasia agreed, urging ongoing discussion with patients “to get them through today.” In fact, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the Society of Gynecologic Oncologists recommend genetic testing for all women with ovarian, fallopian tube, and peritoneal carcinoma. Palliation of symptom management is very important from day 1, declared Dr Monk. Ms Anastasia agreed, urging ongoing discussion with patient to get them through today.
Although most women with advanced ovarian cancer will not be cured, many will live 5-10 years, even while receiving multiple lines of chemotherapy. Reassessing patients goals and initiating palliative and supportive care services can assist with improving quality of life and length of life. n
Disclosure: Dr. Monk has served as an advisor or consultant for Advaxis, Amgen, AstraZeneca, Cerulean, Genentech, GlaxoSmithKline, Gradalis, Merck, Roche, Tesaro, and Verastem. He has served as a speaker for AstraZeneca, Genentech, and Roche and his institution has received grants for clinical research from Amgen, Array BioPharma, Genentech, Janssen/Johnson & Johnson, Lilly, Novartis, and Tesaro. Ms. Anastasia has served on speakers bureaus for Amgen, Genentech, and ProStrakan.
1. Monk B, Anastasia P: Ovarian cancer: Current treatment and patient management. JADPRO Live at APSHO. Track: Solid Tumor Session. Presented November 7, 2015.
2. Kehoe S, Hook J, Nankivell M, et al: Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: Results from the MRC CHORUS trial. 2013 ASCO Annual Meeting. Abstract 5500.
3. Kehoe S, Hook J, Nankivell M, et al: Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS). Lancet 386:249-257, 2015.
4. Katsumata N, Yasuda M, Isonishi S, et al: Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016). Lancet Oncol 14:1020-1026, 2013.
5. Tewari D, Java JJ, Salani R, et al: Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer. J Clin Oncol 33:1460-1466, 2015.
6. Burger RA, Brady MF, Bookman MA, et al: Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365:2473-2483, 2011.
7. Perren TJ, Swart AM, Pfisterer J, et al: A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365:2484-2496, 2011.