Increased efficacy in systemic control

James Fleck: Anticancerweb 15(12), 2019

Data update from the International Agency for Research on Cancer (IARC) revealed the global epidemiological relevance assumed by ovarian cancer. Among gynecological malignancies, ovarian cancer ranks third in incidence (ASR = 6.6) and mortality (ASR = 3.9). The information could be even skewed due to the high incidence and mortality from cervical cancer observed in developing and underdeveloped countries. Recent improving acuity in cervical cancer screening with digitized images and artificial intelligence may change this scenario. Advances in cervical cancer early diagnosis will promote ovarian cancer to the second position in incidence and mortality from gynecological cancer, worldwide. Unfortunately, non-effective screening methods for ovarian cancer lead to an early stage diagnosis in only 25% of the cases. Most patients (75%) are diagnosed at locally advanced (III) or metastatic (IV) disease. Although total hysterectomy plus bilateral salpingo-oophorectomy is the standard primary treatment for early stage ovarian cancer, the benefit of secondary cytoreduction surgery remains controversial. The current use of bevacizumab or PARP (polyadenosine diphosphate-ribose polymerase) inhibitors in the treatment of relapsed platinum-sensitive ovarian cancer has raised additional doubts about the potential benefit of secondary cytoreduction surgery.

In November 2019, the New England Journal of Medicine publishes the results of the GOG-0213 study. This is a multicenter prospective randomized phase III trial in which patients with non-platinum-resistant relapsed ovarian carcinoma showing resectable disease are distributed to an arm treated with cytoreduction surgery + systemic treatment versus an arm subjected to exclusive systemic treatment. Based on study design, one of the objectives was to verify the benefit of combining bevacizumab with chemotherapy, both as induction and maintenance treatment strategies. Another objective was to evaluate the benefit achieved with optimal cytoreduction surgery. Chemotherapy + bevacizumab treatment was administered to 84% of the patients, well-distributed in both arms. The most used chemotherapy program (69% of patients) was paclitaxel + carboplatin combination. In the cytoreduction arm, 67% of the patients reached the condition of complete intraoperative resection. A previous Lancet Oncology publication in June 2017, after a median follow-up of 49.6 months, showed an increase in median overall survival favoring patients treated with bevacizumab + chemotherapy (42.2 months) compared to exclusive chemotherapy (37.3 months) (HR = 0.83 and a P = 0.056). This difference was magnified in a sensitivity analysis based on a treatment-free-time stratification. The most recent publication is focused on the impact of cytoreduction surgery. Progression-free survival was numerically higher in the cytoreduction arm, however an HR = 0.82 for disease progression and death did not confirmed the benefit. Surgery did not increase overall survival, even in the group of patients with complete intraoperative response. Authors' critical analysis of the GOG-0213 trial admitted eventual selection bias. A safe definition of a therapeutic standard for patients with non-platinum-resistant ovarian carcinoma waits for mature results of other ongoing prospective clinical trials.

ASR = Age standardized rate

References:

Robert L. Coleman, Nick M. Spirtos, Danielle Enserro, et al: Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer, N Engl J Med, N Engl J Med 381:1929-39, 2019

Robert L Coleman, Mark F Brady, Thomas J Herzog, et al: Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial, Lancet oncol 18(6): 779-791, 2017