The United States Food and Drug Administration approved several maintenance therapies over the last few years for the management of platinum-sensitive recurrent ovarian cancer. Bevacizumab (Avastin), TKIs, or PARP inhibitors were among the treatments used in the clinical trials leading to these approvals.
Jonathan Foote, MD
The United States Food and Drug Administration (FDA) approved several maintenance therapies over the last few years for the management of platinum-sensitive recurrent ovarian cancer. Bevacizumab (Avastin), TKIs, or PARP inhibitors were among the treatments used in the clinical trials leading to these approvals.
Investigators from a variety of cancer centers used the American Society of Clinical Oncology (ASCO)’s Net Health Benefit (NHB) and the European Society of Medical Oncology (ESMO)’s Magnitude of Clinical Benefit Scale (MCBS) to identify the value of each maintenance therapy and biomarker to direct treatment. The centers involved in this included Duke University Medical Center, David Geffen School of Medicine at UCLA in Los Angeles, The Ohio State University, James Cancer Hospital in Columbus, Ohio, and Memorial Sloan Kettering Cancer Center in New York City, New York.
Clinical benefit, toxicity, long-term survival, palliation of symptoms, treatment-free interval, and quality of life can be found with the NHB with a total possible score of 180.
MCBS examines the clinical benefit grade, early stopping of crossover, toxicity, quality of life, and adjustments. The highest possible grade for the MCBS is a 4, which the ESMO considers to be a high-value grade.
Investigators evaluated maintenance trials in ovarian cancer, particularly in the OCEANS and GOG 213 trials for bevacizumab treatments, ICON6 for cediranib, a TKI, and the Study 19, NOVA, SOLO2, and ARIEL3 trials in order to understand a select variety of PARP inhibitors.
According to the findings that were presented at the 49th Society of Gynecologic Oncology (SGO) Annual Meeting on Women's Cancers that took place in New Orleans from March 24-27, a higher ASCO and ESMO value assessment was found in women with germline- or somatic-BRCAmutations or tumor homologous recombination deficiency (HRD) who were positivity treated with a PARP inhibitor.
In the OCEANS trial, the composite value scores of ASCO for concurrent plus maintenance bevacizumab were 35. In the GOG 213 trial, there was a score of 26. The ICON6 trial found a TKI ASCO composite score of 30. ESMO’s value grades were also comparable to these.
SOLO2, Study 19, NOVA, and ARIEL3 trials found targeted composite value comparison for germline and somatic BRCA mutations in the PARP inhibitor with a range of 47 to 62.
“These are the highest value scores observed in maintenance therapy for platinum-sensitive recurrent ovarian cancer,” said Jonathan Foote, MD, Duke University Medical Center in Durham, North Carolina.
The composite values for ASCO and ESMO were compared for patients with wild-typeBRCA, HRDs, and germline and somaticBRCAmutations. Scores ranged from 26 to 62 in the PARP inhibitor trials, while ESMO scores were similar. The ASCO scores for non-biomarker-based PARP inhibitors and bevacizumab were comparable as well, noted Foote.
However, there were some limitations to the study. Foote explained, “ASCO and ESMO value scores are not intended to compare clinical trials to each other. However, we found that comparing the relative value of treatments using these tools is a very objective measure of benefit that can be used to counsel patients.”
There was no allowance for incorporation of both progression-free survival and overall survival data in value frameworks and cost was not considered. An unknown effect of biomarker status in patients was also found in other undergoing maintenance therapies besides PARP inhibitors.
According to ASCO, genetic testing was deemed beneficial in terms of patient management, such as surgical treatment, prognosis and risk for additional cancers. This will also help in creating individualized patient care and shared decision making.
“Our data highlights the importance of germline and somaticBRCAtesting to differentiate treatment value and to assist in treatment decisions,” noted Foote.
Foote JR, Alvarez-Secord A, Liang MI, et al. Bevacizumab, TKI, or PARPi? A targeted approach using composite value-based endpoints and biomarkers to individualize care for platinum-sensitive recurrent ovarian cancer (PSROC). Presented at: SGO Annual Meeting on Women’s Cancer; March 24-27, 2018. New Orleans.Abstract 19.