Outcomes and endpoints of relevance in gynecologic cancer clinical trials

Abstract

Drug development is paramount to improve outcomes in patients with gynecologic cancers. A randomized clinical trial should measure whether a clinically relevant improvement is detected with the new intervention compared with the standard of care, using reproductible and appropriate endpoints. Clinically meaningful improvements in overall survival and/or quality of life (QoL) are the gold standards to measure benefit of new therapeutic strategies. Alternative endpoints, such as progression-free survival, provide an earlier measure of the effect of the new therapeutic drug, and are not confounded by the effect of subsequent lines of therapy. Yet, its surrogacy with improved overall survival or QoL is unclear in gynecologic malignancies. Of relevance to studies assessing maintenance strategies are other time-to-event endpoints, such as progression-free survival two and time to second subsequent treatment, which provide valuable information on the disease control in the longer term. Translational and biomarker studies are increasingly being incorporated into gynecologic oncology clinical trials, as they may allow understanding of the biology of the disease, resistance mechanisms, and enable a better selection of patients who might benefit from the new therapeutic strategy. Globally, the endpoint selection of a clinical trial will differ according to the type of study, population, disease setting, and type of therapeutic strategy. This review provides an overview of primary and secondary endpoint selection of relevance for gynecologic oncology clinical trials.

Novel therapies leading to a new landscape in gynecologic tumors

“…In the past decade, we have witnessed notable advances in gynecologic cancer research, from the laboratory to the clinic, including therapeutics targeting DNA damage repair, immune checkpoint inhibitors, and antibody drug conjugates 1–5. This is an unprecedented time of rapid shift in gynecologic oncology drug development, as manifested by an expanding list of new therapies for cervical, endometrial, and ovarian cancer.…”

“…The introduction of immune checkpoint inhibitors in endometrial and cervical cancer is another relevant shift in the therapeutic landscape of gynecologic cancers 1 4. As an example, front line pembrolizumab, in combination with standard of care chemotherapy (with or without bevacizumab), has shown improvements in overall survival and quality of life in patients with advanced or recurrent cervical cancer compared with placebo 3,4…”

“…The future is bright in the treatment of gynecologic cancers with the discovery of novel therapeutics that have provided clinically meaningful improvements in patients outcomes 3. But it is important to recognize that there is much more to do, and social and racial inequities in prevention and cancer care need to be addressed 1.…”

“…In the past decade, we have witnessed notable advances in gynecologic cancer research, from the laboratory to the clinic, including therapeutics targeting DNA damage repair, immune checkpoint inhibitors, and antibody drug conjugates. [1][2][3][4][5] This is an unprecedented time of rapid shift in gynecologic oncology drug development, as manifested by an expanding list of new therapies for cervical, endometrial, and ovarian cancer. Furthermore, research and innovation in less common tumors, such as gestational trophoblastic tumors, low grade serous, and clear cell ovarian carcinoma have also revealed new therapeutic opportunities, optimizing efficacy, and reducing potential toxicity.…”

“…1 4 As an example, front line pembrolizumab, in combination with standard of care chemotherapy (with or without bevacizumab), has shown improvements in overall survival and quality of life in patients with advanced or recurrent cervical cancer compared with placebo. 3,4 The future is bright in the treatment of gynecologic cancers with the discovery of novel therapeutics that have provided clinically meaningful improvements in patients outcomes. 3 But it is important to recognize that there is much more to do, and social and racial inequities in prevention and cancer care need to be addressed.…”