Landmark Trials in Selected Gynecologic Cancers

Abstract

This chapter contains a summary of some key findings from a selection of 34 trials related to endometrial, cervical, ovarian, and vulvar cancer.

In endometrial cancer, the 13 trials include a study by Creasman et al. that helped establish predictive factors for lymph node metastasis. Five trials that evaluated adjuvant brachytherapy and/or external beam radiation therapy in patients with surgically resected endometrial cancer are discussed including the Norwegian trial by Aalders et al., PORTEC-1, PORTEC-2, GOG 99, and the Swedish trial by Sorbe et al. Panici et al. and the ASTEC trial studied the role of pelvic lymphadenectomy and are included. Multiple trials that addressed adjuvant management in high-risk and advanced endometrial cancer are discussed including trials by Maggi et al., GOG 122, RTOG 97–08, a combined analysis of NSGO/EORTC and MaNGO ILIADE-3, and PORTEC-3.

In cervical cancer, the ten trials that are discussed include a 9vHPV vaccine trial by Joura et al. to highlight the importance of vaccination in preventing HPV-induced malignancy. The Landoni et al. single-institution trial that evaluated surgery versus radiation therapy for early-stage disease and the LACC trial that compared surgical techniques for early-stage patients are included. GOG 92 and GOG 109 helped establish postoperative management criteria for radiotherapy or chemoradiotherapy and are discussed. Also included are two meta-analyses by Green et al. and the Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration that compared outcomes with radiation therapy alone versus chemoradiotherapy for cervical cancer. In the advanced cervical cancer setting, GOG 204 compared four cisplatin doublet regimens, and GOG 240 evaluated the role of bevacizumab, and both trials are discussed. Finally, intensity-modulated radiation therapy technique was compared to standard radiation therapy technique by Klopp et al. in the postoperative setting for patients with cervical and endometrial cancer and is included.

In ovarian cancer, eight trials are discussed including GOG 172 as representative of trials that have studied the role of intraperitoneal chemotherapy. Three trials that evaluated the optimal chemotherapy regimen and how it should be sequenced including JCOG 3016, Gynecologic Cancer InterGroup (Vergote et al.), and the MITO-7 trial are discussed. Both GOG 218 and ICON-7 studied the role of bevacizumab and are included. The GOG 262 evaluated both the role of bevacizumab and the optimal chemotherapy schedule and is discussed. Finally, the SOLO1 trial studied the role of the polyadenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib for patients with stage III or IV high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with mutation in BRCA1 and/or BRCA2 and is included.

Vulvar cancer is much less common than the other malignancies discussed in this chapter, and three trials are included. The GROINSS-V-1 trial was the largest prospective observational trial that included sentinel node biopsy as part of management and is included. GOG 205 was a phase 2 trial that evaluated the role of chemoradiotherapy in selected patients with locally advanced disease. Finally, GOG 37 compared ipsilateral pelvic node resection to pelvic radiation therapy and is discussed.

There are hundreds of trials to choose from, and therefore, no claim toward completeness can be made in the current format. These trials relate to the multidisciplinary management of gynecologic malignancies from the perspective of a radiation oncologist. Readers are encouraged to refer to the full manuscript of these trials for a greater understanding. This material is provided for educational purposes only and with the goal of encouraging further study about the landmark trials that have impacted oncology.