Cara Mathews, MD, Details Results of Dostarlimab Vs Historical Control Data in Advanced Endometrial Cancer

In a poster presentation from Society of Gynecologic Oncology 2022 Annual Meeting, investigators led by Cara Mathews, MD, aimed to determine the benefit of dostarlimab vs standard-of-care doxorubicin for advanced recurrent endometrial cancer.

Patients with advanced recurrent endometrial cancer receiving treatment with dostarlimab (Jemperli) appeared to have better outcomes vs historical control data of doxorubicin in this setting, according to data made available at The Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer.

Results from the phase 1 GARNET trial (NCT02715284) were compared with those of doxorubicin therapy in patients with second-line endometrial cancer from a phase 3 trial, showing a statistically significant 59% reduction in the risk of disease progression or death with the PD-1 inhibitor (HR, 0.41; 95% CI, 0.28-0.61; P <.0001).

Additionally, a statistically significant benefit to progression-free survival (PFS) was noted with dostarlimab vs doxorubicin (HR, 0.38; 95% CI, 0.28-0.51; P <.0001). Corresponding objective response rates were 43.5% (95% CI, 33.2%-54.2%) and 13.7% (95% CI, 9.6%-18.8%), with an adjusted odds ratio of 0.19 (95% CI, 0.11-0.33; P <.0001).

GARNET is an ongoing phase 1 trial examining dostarlimab in patients with advanced solid tumors. In the current analysis, patient-level data in those with mismatch repair deficient (MMRd)/microsatellite instability–high endometrial cancer from cohort A1 were pooled with those of the phase 3 ZopteC trial (NCT01767155) control arm, which comprised doxorubicin only in second-line endometrial cancer.

In an interview with CancerNetwork®, Cara Mathews, MD, a gynecologic oncology specialist at the Women and Infants Hospital of Rhode Island, spoke about comparing the results from both trials and why it may be beneficial to use historical data in this context rather than randomized controlled trials.

CancerNetwork®: What was the rationale for assessing dostarlimab in patients with advanced and recurrent endometrial cancer?

Mathews: Endometrial cancer has historically been a disease where we had very few treatment options when patients recur. Typically, we’ve used traditional chemotherapy in the advanced recurrent setting, but outcomes are abysmal and therapy is toxic. This is a space for which we’ve made gains recently and continue to need to make gains. That was the rationale for looking at dostarlimab in this population.

What were some of the key findings from this research?

The project that we presented at the meeting is looking at patients who are MMRd, so typically [those with microsatellite unstable disease], who are treated with single-agent dostarlimab which is a PD-1 inhibitor compared with patients from the ZopteC trial, who were treated on a matched standard doxorubicin arm. We had patient level data and were able to compare [outcomes from] 2 clinical trial settings where we had good data.

This is a novel trial method and it’s important because for dostarlimab the outcomes have been so promising that it would be hard to do a head-to-head comparison for this treatment vs standard chemotherapy. Some would even argue that it might be unethical at this point [to perform a randomized controlled trial], so we can use these data from these 2 populations and compare the PD-1 inhibitor vs standard chemotherapy. The results were really exciting and showed that, not surprisingly, dostarlimab performed very well. [Median] PFS between the 2 arms showed a clear benefit to dostarlimab [at] 12.2 months vs 4.9 months. For overall survival, the doxorubicin arm was 11.2 months and it wasn’t reached in the dostarlimab. Survival and outcomes were clearly beneficial for the PD-1 inhibitor in this population.

How did the toxicity profiles of both treatments compare?

Overall, dostarlimab has been very well tolerated and there were more hematologic toxicities in the standard chemotherapy arm which is probably not surprising to most clinicians who are using these 2 medications now. Notably, there was more fatigue in the dostarlimab arm.

Do you see these results potentially impacting the treatment landscape?

This gives further support to the idea of using PD-1 inhibition in the frontline recurrent setting—not in frontline treatment but in the first recurrence for this population. That is consistent with what we’re seeing across different clinical trials at this point.

Where do you think that future research efforts are going to be focused?

The response rate in this treatment arm for the [patients MSI-high tumors] treated with dostarlimab is over 40%, but that leaves about 60% of patients in that cohort who didn’t respond. [Addressing those patients] is probably our future direction—trying to figure out who responded va who didn’t. How can we take those nonresponders and make them responders in the future?

What do you hope your colleagues took away from the presentation?

It is important for us to realize how what we think of as a standard of care is actually very toxic as well. Continuing to find new treatments that are better than the old and are working for this patient population [should be the goal].

Were there any other presentations at this year’s meeting that you were particularly excited for?

Some of the endometrial talks [about targeted agents] were really exciting and interesting. It just shows how far we’ve come in a short period of time. Since I finished fellowship 10 years ago, this treatment landscape has completely changed, and our project is part of that.

Reference

Mathews C, Lorusso D, Coleman RL, et al. The comparative clinical effectiveness of dostarlimab versus doxorubicin in the treatment of advanced/recurrent endometrial cancer. Presented at: 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022. Phoenix, Arizona.