The Highlights: Advances in Screening and Management of Ovarian Cancer

285 OVhighlights

News from annual meetings of the Society of Gynecologic Oncology and the American Society of Clinical Oncology

By Krishnansu S. Tewari, MD, FACOG, FACS

 

Society of Gynecologic Oncology

The 44th Annual Meeting on Women’s Cancer was held by the Society of Gynecologic Oncology (SGO, formerly Society of Gynecologic Oncologists) in Los Angeles from March 9 to 12, 2013. This meeting brought together more than 1,000 gynecologic oncologists from all over the world, along with other healthcare professionals interested in the management of gynecologic malignancies. Three of the most important studies presented during the plenary sessions related to ovarian cancer.

 

In a Surveillance Epidemiology and End Results (SEER) study in California, researchers found that most women with ovarian cancer undergoing surgery in the state were being operated on by surgeons who were not trained to perform the type of operation required to adequately stage patients and completely remove all visible disease when it has been found to spread throughout the abdominal cavity.1 Only one-third of the patients studied were referred to and treated by gynecologic oncologists who were considered high-volume surgeons or characterized as having completed more than 10 to 15 cases per year in institutions doing more than 20 cases per year. It is difficult to determine whether the issue is lack of access to gynecologic oncologists, refusal of the gynecologist to refer the patient, or the gynecologist’s belief that the patient did not have cancer.

The researchers also found that most study participants were not treated according to National Comprehensive Cancer Network (NCCN) guidelines and specifically that patients with Stage I and Stage II disease who were not treated according to NCCN guidelines had worse survival rates compared with those who were. Survival was also worse for patients with advanced-stage cancers who weren’t treated according to NCCN guidelines.

The second key presentation was the long-term follow-up of two Phase III randomized trials of intraperitoneal-intravenous chemotherapy in women with ovarian cancer.2 The original studies were published in 2001 and 2006, and now, with nine to 10 years of follow-up, data demonstrated that the findings of increased overall survival in patients treated with intraperitoneal-intravenous therapy were sustained. Unfortunately, intraperitoneal therapy has still not caught on throughout the country for various reasons, including concerns about toxicity, the labor-intensive process, and a lack of training, among others. The Gynecologic Oncology Group (GOG) is addressing the toxicity concerns in a Phase III randomized trial that recently completed accrual (protocol 252).

The third integral study from the SGO on ovarian cancer was an ancillary data analysis of GOG protocol 218, which was a Phase III randomized trial evaluating the integration of the anti-angiogenesis drug bevacizumab in the upfront management of women who had undergone surgical debulking for newly diagnosed epithelial ovarian cancer.3 The data presented evaluated whether time to initiation of chemotherapy from the point of surgery was important. Researchers found that there was a window of opportunity of 25 days wherein if chemotherapy were not initiated, outcome was worse. The timing was much more important in the group of patients who had the most successful surgeries, leaving only microscopic residual disease. It is unclear why delays in starting therapy occurred, but this may have been due to postoperative complications, the referral process, or getting to a medical oncologist if the gynecologic oncologist wasn’t administering the chemotherapy. Because surgery is so important in this group of patients, we need some mechanism whereby chemotherapy can be instituted quickly because this group of patients is the most sensitive.

Although not formally presented at the Annual Meeting on Women’s Cancer this year, a prospective, multi-institutional trial was published in the SGO’s official journal, Gynecologic Oncology, to coincide with the meeting. The trial was designed to validate the effectiveness of the OVA1 test (a blood test designed to evaluate ovarian tumors for malignancy) in identifying ovarian malignancy compared with clinical assessment and a CA-125 II blood test among women undergoing surgery for an adnexal mass.4 The manuscript was included in the meeting materials provided to attendees and reported that OVA1 demonstrated higher sensitivity (95.7 percent) and negative predictive value (98.1 percent) compared with clinical impression and the CA-125 II.

 

American Society of  Clinical Oncology

The 49th Annual Meeting of the American Society of Clinical Oncology (ASCO) was held from May 31 to June 4, 2013, in Chicago and brought together more than 35,000 oncologists, healthcare professionals, and industry representatives from all over the world. ASCO remains the largest annual meeting in the world of cancer screening, diagnosis, treatment, and follow-up. Each disease system has its own track for plenary presentation and poster discussion, and several noteworthy studies in ovarian cancer were presented this year.

Phase I data from the UK Familial Ovarian Cancer Screening Study showed that annual transvaginal ultrasound (TVS) and CA-125 screening in women at high risk of ovarian and fallopian tube cancer lacked sensitivity for early-stage disease but may result in improved optimal debulking rates when patients were taken to surgery.5 It was thought that more-frequent screening might provide greater benefits, so a Phase II study (the largest of its kind) was conducted. For five years 4,531 women at high risk of ovarian and fallopian tube cancer were recruited and screened at 42 UK centers. CA-125 blood tests were analyzed every four months via the risk of ovarian cancer algorithm; TVS was analyzed annually. The study reported that the more-frequent-than-annual screening data constitute further evidence of a beneficial effect on success of debulking surgery, which may translate into improved survival.

In the therapeutic arena, it was reported last year that adding the anti-angiogenesis agent bevacizumab to chemotherapy significantly improved the time to relapse in patients with platinum chemotherapy–resistant ovarian cancer. At this year’s ASCO meeting, the impact on quality of life of adding this drug was reported.6 Investigators found that adding bevacizumab to chemotherapy led to greater than 15 percent improvement in patient-reported abdominal and gastrointestinal symptoms, most likely because patients felt better overall as the cancers shrunk with therapy.

Using another anti-angiogenesis agent, the oral drug pazopanib, researchers performed a randomized placebo-controlled clinical trial to determine whether the drug delayed recurrence in women who had been in remission following surgery and chemotherapy for newly diagnosed ovarian cancer.7 More than 900 patients enrolled in this trial, and the research team reported that those patients who received pazopanib had a significantly delayed time before they relapsed—meaning they lived cancer-free longer than those who received the placebo.

 

Finally, in a novel clinical trial involving another oral drug, called olaparib, researchers found that patients with chemotherapy-sensitive relapsed ovarian cancer and an inherited BRCA mutation that predisposes patients to breast and ovarian cancer are most likely to have a delayed relapse when the drug is given as a maintenance therapy (similar to pazopanib above) after patients have attained remission with no detectable signs of ovarian cancer.8

 

References

1. Bristow RE, Chang J, Ziogas A, et al. NCCN treatment guidelines for ovarian cancer: A population-based validation study of structural and process quality measures. Paper presented at: 44th Annual Meeting on Women’s Cancer by the Society of Gynecologic Oncology; March 9–12, 2013; Los Angeles, CA. Abstract 45.

2. Tewari D, Java J, Salani R, et al. Long-term survival advantage of intraperitoneal chemotherapy treatment in advanced ovarian cancer: an analysis of a Gynecologic Oncology Group ancillary data study. Paper presented at: 44th Annual Meeting on Women’s Cancer by the Society of Gynecologic Oncology; March 9–12, 2013; Los Angeles, CA. Abstract 6.

3. Eskander R, Java J, Tewari KS, et al. Negative survival impact associated with >25 day interval from surgical cytoreduction to initiation of systemic therapy in advanced ovarian carcinoma: a Gynecologic Oncology Group ancillary data study. Paper presented at: 44th Annual Meeting on Women’s Cancer by the Society of Gynecologic Oncology; March 9–12, 2013; Los Angeles, CA. Abstract 56.

4. Bristow RE, Smith A, Zhang Z, et al. Ovarian malignancy risk stratification of the adnexal mass using a multivariate index assay. Gynecologic Oncology 2013;128(2):252-59.

5. Rosenthal N, Fraser L, Philpott S, et al. Final results of 4-monthly screening in the UK Familial Ovarian Cancer Screening Study (UKFOCSS Phase 2). Journal of Clinical Oncology. 2013;31(suppl; abstr 5507).

6. Stockler R, Hilpert F, Friedlander M, et al. Health-related quality of life (HRQoL) results from the AURELIA trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum-resistant recurrent ovarian cancer (OC). Journal of Clinical Oncology. 2013;31(suppl; abstr 5542).

7. Du Bois A, Floquet A, Kim JW, et al. Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): Results of an international intergroup trial (AGO-OVAR16). Journal of Clinical Oncology. 2013;31(suppl; abstr LBA5503).

8. Ledermann JA, Harter P, Gourlev C, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer (SOC) and a BRCA mutation (BRCAm). Journal of Clinical Oncology. 2013;31(suppl; abstr 5505).