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Top ASCO Abstracts in Ovarian
ASCO 2017: My Top Clinically Relevant Ovarian Cancer Abstracts

Released: July 11, 2017

Expiration: July 10, 2018

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The 2017 ASCO Annual Meeting featured multiple important phase II and phase III gynecologic cancer studies. In this commentary, I discuss my top abstract picks in ovarian cancer that I feel have the most potential to influence clinical practice.

Surgery in Ovarian Cancer
Bulk-reducing surgery remains a backbone of ovarian cancer treatment despite advances in neoadjuvant chemotherapy. Three abstracts selected for oral presentation focused on this setting for ovarian cancer. The decision to perform systemic lymphadenectomy at the time of primary surgical debulking after achieving complete resection (R0) is controversial. The Lymphadenectomy in Ovarian Neoplasms (LION) study was a prospective, randomized phase III trial of lymph node dissection (LND) in patients with advanced (stage IIB-IV), resectable ovarian cancer. Intraoperatively, the patients had to have a complete resection and clinically negative nodes (N = 647). These patients were randomized to systematic pelvic and periaortic LND vs no further surgery. Results showed longer operative time and significantly more blood loss, transfusions, ICU care, postoperative antibiotics, and repeat laparotomies for complications in the LND group. The primary endpoint of OS showed no significant difference: Median OS was 65.5 months with LND vs 69.2 months without LND (P = .65). Likewise, median PFS was 25.5 months in both arms. These data demonstrate the lack of benefit of systematic LND in patients with complete cytoreduction for ovarian cancer, and the authors suggest that this procedure be omitted to spare patients the increased morbidity.

Another surgical conundrum in ovarian cancer is the question of secondary cytoreduction for patients who have experienced a significant disease-free interval after initial treatment. Du Bois and colleagues conducted the phase III AGO DESKTOP III/EnGOT ov20 study, which was designed to provide a clearer answer to this clinical challenge. This study was the third DESKTOP trial and used the AGO score developed in DESKTOP I and validated as a predictive marker of complete resection in DESKTOP II. Eligible patients for the current study (N = 408) had platinum-sensitive recurrent ovarian cancer, defined as recurrence 6 months or longer after completion of platinum therapy, and a positive AGO score (ECOG PS 0, R0 at the time of first debulking surgery, and ascites ≤ 500 mL). Patients were randomized to receive cytoreduction with maximal effort or no cytoreduction prior to platinum-based chemotherapy. Results showed complete macroscopic resection in 72.5% of patients in the surgery arm. Data for the primary endpoint, OS, were not yet mature at the time of presentation, but median PFS was prolonged by 5.6 months with the addition of surgery to chemotherapy (19.6 vs 14.0 months for chemotherapy alone; P < .001). However, longer PFS was only seen in those patients who had complete resection of macroscopic disease. Remarkably, there was no significant difference in mortality rates at 30, 60, 90, or 180 days, suggesting that cytoreductive surgery is safe for the selected patient population. One caveat for this study is that because RECIST 1.1 is used to assess progression, it systematically biased the median PFS in favor of the surgery cohort (as target lesions were presumably removed during cytoreduction) and, therefore, the primary endpoint of OS is needed to truly evaluate the clinical efficacy. Presenting the secondary endpoint of PFS prior to maturity of the primary endpoint of OS is unusual. Thus, level 1 evidence for secondary cytoreduction remains elusive.

Finally, bevacizumab has been studied as part of primary ovarian cancer therapy in the phase III GOG 218 trial, but its use in the neoadjuvant setting and the potential effect on surgical outcomes at the time of interval debulking surgery has not been adequately studied. Garcia and colleagues conducted the phase II GEICO 1205/NOVA trial exploring the addition of bevacizumab to neoadjuvant chemotherapy in advanced ovarian cancer. Eligible patients with no evidence of intestinal occlusion (N = 68) were randomized to 4 cycles of carboplatin and paclitaxel, with or without bevacizumab, prior to planned interval cytoreduction. Following surgery, all patients were given 3 cycles of adjuvant carboplatin, paclitaxel, and bevacizumab (1 did not receive bevacizumab) plus maintenance bevacizumab for 15 months. The primary endpoint was the complete macroscopic response rate (ie, peritoneal cancer index score of 0) at the time of interval cytoreduction. Unfortunately, fewer than 10% of patients had a complete macroscopic response, and there was no difference between the groups. There was an improvement in the rate of surgical feasibility, as measured by the surgeons, but no improvement in complete cytoreduction or median PFS (~ 20 months in both groups). There were significantly fewer grade 3 AEs in the bevacizumab group; that said, the sole death on study was due to postoperative sepsis in a patient receiving neoadjuvant bevacizumab. The authors note that their data support the use of neoadjuvant bevacizumab in select high-risk patients. However, without an improvement in surgical complete resection or median PFS, this strategy may not be widely adopted given the cost of bevacizumab.

Targeted Therapy in Relapsed Ovarian Cancer
Targeting defective DNA damage repair using PARP inhibitors has demonstrated excellent improvements in ovarian cancer therapy. The results of the phase III SOLO2 study of maintenance therapy with the PARP inhibitor olaparib in platinum-sensitive, relapsed ovarian cancer were reported at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in March 2017. This study enrolled 295 patients with germline BRCA1/2 mutations who had a CR to platinum-based chemotherapy after at least 2 lines of treatment. The median PFS with olaparib was 19.1 months vs 5.5 months for placebo. Although clearly outstanding results, olaparib must be taken orally every day, often for many months or years, which may affect health-related quality-of-life (HRQoL).

Friedlander and colleagues reported the preplanned HRQoL assessment from SOLO2 using the change in the Trial Outcome Index, an established and validated single-targeted index derived from the Functional Assessment of Cancer Therapy—Ovarian (FACT-O), a patient-reported questionnaire specific to ovarian cancer–related symptoms. The authors reported no significant detrimental effect of olaparib vs placebo on HRQoL. Patients reported feeling “relatively well” with no significant decrease in this report over 12 months. Despite the relative toxicity of olaparib, the quality-adjusted PFS remained significant: 13.96 months with olaparib vs 7.28 months with placebo (P < .0001). Of most importance, the use of maintenance olaparib delayed the onset of disease-related symptoms associated with recurrent ovarian cancer compared with those receiving placebo: 13.5 months vs 7.21 months (P < .0001). These data represent an important step forward in understanding and quantifying the tradeoffs patients experience during maintenance therapy with olaparib. [NOTE: On August 17, 2017, the FDA approved olaparib tablets for maintenance treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in CR or PR to platinum-based chemotherapy.]

Angiogenesis inhibitors provide another area of tumor targeting in ovarian cancer. Ledermann and colleagues presented the final analysis of ICON6, a randomized, controlled phase III study of upfront chemotherapy with or without the pan-VEGF inhibitor cediranib in platinum-sensitive, relapsed ovarian cancer after primary cytoreduction and adjuvant platinum-based chemotherapy. Participants (planned N = 2000) were randomized to chemotherapy plus either placebo continued through the maintenance phase, cediranib 20 mg daily followed by placebo maintenance, or cediranib followed by cediranib maintenance. Of note, the sponsor discontinued development of cediranib in 2011, which led to a redesign of the study with fewer patients (N = 440) and a primary endpoint comparing median PFS in patients receiving chemotherapy plus placebo vs chemotherapy plus cediranib followed by cediranib maintenance. The PFS data presented in 2013 demonstrated an improvement of 2.4 months (HR: 0.57; 95% CI: 0.45-0.74). In the presentation of final OS data at ASCO 2017, the difference in median OS was 7.4 months in favor of the addition of cediranib. Unfortunately, the study was unavoidably underpowered and did not reach the planned statistical endpoint (P = .21). Further investigation of maintenance cediranib plus olaparib is under way in ICON 9.

These trials demonstrate the continued importance of careful surgery and the ever-increasing power of novel therapy for ovarian cancer. These and other important studies reported at ASCO 2017 have brought considerable attention to continued advances in the treatment of gynecologic cancers.

Please share your top ASCO picks or any questions on current management approaches for patients with ovarian cancer in the comment box below.