Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab ± Olaparib as a First-Line Treatment for 

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab ± Olaparib as a First-Line Treatment for Newly Diagnosed Advanced or Recurrent Endometrial Cancer: Results From the Phase III DUO-E/GOG-3041/ENGOT-EN10 Trial

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Shannon Westin, MD, reviews the results of the Phase III DUO-E/GOG-3041/ENGOT-EN10 trial in patients with newly diagnosed advanced or recurrent endometrial cancer.

Shannon Westin, MD, MPH, FACOG, director, Early Drug Development, professor, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, discusses key data on the use of durvalumab (Imfinzi) plus chemotherapy followed by durvalumab and olaparib (Lynparza) maintenance in the phase 3 DUO-E trial (NCT04269200) of patients with newly diagnosed advanced or recurrent endometrial cancer.

The DUO-E trial assessed the efficacy of combining durvalumab with chemotherapy in patients with newly diagnosed, stage III/IV recurrent endometrial cancer who had not previously received systemic treatment. Patients were randomly assigned 1:1:1 to one of 3 groups: carboplatin and paclitaxel alone, carboplatin and paclitaxel plus durvalumab, or carboplatin and paclitaxel with both durvalumab and olaparib. The primary end point was progression-free survival (PFS), with overall survival (OS) as a secondary end point.

In the intent-to-treat population, both durvalumab combination regimens produced a statistically significant and clinically meaningful improvement in PFS compared with chemotherapy alone, meeting its primary end point, Westin reports. The median PFS increased from 9.6 months (95% CI, 9.0-9.9) in the control group to 10.2 months (95% CI, 9.7-14.7) with the durvalumab and chemotherapy regimen and 15.1 months (95% CI, 12.6-20.7) with the durvalumab and olaparib regimen, she details. Corresponding hazard ratios for the durvalumab and durvalumab plus olaparib arms vs the control arm were 0.71 (95% CI, 0.57-0.89; 

<.0001), respectively. These translated to respective reductions in the risk of disease progression or death of 29% and 45%, Westin says.

Although the interim OS data were not fully mature at the time of the interim analysis, a trend towards OS improvement was observed in the combined treatment arms compared with chemotherapy alone, Westin continues. At 18 months, OS rates were 79.4%, 74.6% and 69.0% in the durvalumab plus olaparib, durvalumab, and control arms, respectively.

Subgroup analysis based on mismatch repair (MMR) status demonstrated benefits for both mismatch repair–deficient (dMMR) and MMR-proficient (pMMR) patients, Westin adds. Notably, the addition of olaparib to the treatment regimen further enhanced the PFS benefit in pMMR patients, she emphasizes. Regarding safety, the toxicity profiles of both combination treatments were in line with that of the individual agents.

Overall, these findings suggest that combining immunotherapy with chemotherapy is a promising approach to enhance outcomes in patients with advanced endometrial cancer.

Shannon N. Westin, MD, MPH, FACOG, discusses key data on the use of durvalumab plus chemotherapy followed by durvalumab and olaparib maintenance in the phase 3 DUO-E trial of patients with newly diagnosed advanced or recurrent endometrial cancer.

Dr Westin on Durvalumab and Chemotherapy With or Without Maintenance Olaparib in Endometrial Cancer  

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Gaining Ground in Gynecologic and Hematologic Cancers at ASCO 2023: Drs Herrera, Westin, and Jabbour

Shannon N. Westin, MD, MPH, FACOG, director, Early Drug Development and Phase I trials Department, professor, Department of Gynecologic Oncology and Reproductive Medicine, discusses the outcomes of the phase 1b SOLAR trial (NCT05554328), which examined olaparib (Lynparza) with selumetinib (Koselugo) in patients with 

-mutant gynecologic malignancies and other solid tumors.

Within the dose-expansion portion of the trial, investigators examined the combination in 4 different expansion groups: endometrial cancer with 

 pathway activations, ovarian cancer with 

 pathway activations, and ovarian cancer that progressed on a prior PARP inhibitor. 

Findings presented at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer

showed that olaparib plus selumetinib elicited varying degrees of efficacy across the 4 cohorts, with the most exciting data emerging the in 

-mutant endometrial cancer cohorts, Westin explains.

 mutant ovarian cancer cohort experienced an overall response rate (ORR) of 32%, with all responders achieving a partial response (PR), and a clinical benefit rate of 69%. Additionally, those patients within that cohort who had low grade serous ovarian cancer had an ORR of 44%. In the 

-mutant endometrial cancer cohort, the ORR was 35%, with all responders experiencing a PR, and 59% of patients achieved clinical benefit. 

-mutant solid tumor cohort and the PARP-resistant cohort, the benefits were not as prevalent, Westin notes. Two patients with lung cancer experienced a PR in the solid tumor cohort, translating to an ORR of 8%, and the clinical benefit rate was 31%. Notably, among patients with lung cancer, approximately half of these patients achieved a clinical benefit, Westin note. In the PARP-resistant group, the ORR was 17%, and the clinical benefit rate was 42%.

The combination of olaparib and selumetinib is being further explored in patients with RAS-mutant ovarian or endometrial cancer in the ongoing phase 2 ComboMATCH trial (NCT05554328).

Shannon N. Westin, MD, MPH, FACOG, discusses the outcomes of the phase 1b SOLAR trial, which examined olaparib with selumetinib in patients with RAS-mutant gynecologic malignancies and other solid tumors.

Dr Westin on Outcomes of the SOLAR Trial in RAS-Mutant Gynecological Malignances

Shannon N. Westin, MD, MPH, clinical investigator and director of Early Drug Development and Phase I Trials in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, discusses challenges with precision medicine in endometrial cancer. 

Despite encouraging data ​with combination ​regimens such as lenvatinib (Lenvima) and pembrolizumab (Keytruda), ​toxicity remains a challenge, says Westin.

​However, this does not mean that chemotherapy is the better alternative, ​she adds.

Precision medicine shows promise in the endometrial cancer space ​and research efforts are aimed at developing strategies to mitigate or prevent treatment-related adverse effects (AEs), ​Westin says.

Often, patients​ who experience AEs may want to stop treatment, even if the regimen is working. Finding a way to mitigate AEs will help patients remain on effective therapies, Westin concludes. 

Shannon N. Westin, MD, MPH, discusses challenges with precision medicine in endometrial cancer. 

Shannon N. Westin, MD

Articles

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab ± Olaparib as a First-Line Treatment for Newly Diagnosed Advanced or Recurrent Endometrial Cancer: Results From the Phase III DUO-E/GOG-3041/ENGOT-EN10 Trial

Dr Westin on Durvalumab and Chemotherapy With or Without Maintenance Olaparib in Endometrial Cancer

Gaining Ground in Gynecologic and Hematologic Cancers at ASCO 2023: Drs Herrera, Westin, and Jabbour

Dr Westin on Outcomes of the SOLAR Trial in RAS-Mutant Gynecological Malignances

Dr. Westin on Challenges With Precision Medicine in Endometrial Cancer