Immune Checkpoint Inhibitors in Recurrent Endometrial Cancer: Clinical Trial Data

EP: 1.Patient Case: A 64-Year-Old Woman With Recurrent Endometrial Cancer

EP: 2.Endometrial Cancer: Factors in Selecting First- and Second-Line Therapy

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EP: 3.Immune Checkpoint Inhibitors in Recurrent Endometrial Cancer: Clinical Trial Data

EP: 4.Recurrent Endometrial Cancer: An Evolving Treatment Landscape

EP: 5.Combination IO Strategies in Advanced Endometrial Cancer: RUBY and GY018

EP: 6.Single-Agent IO Therapy in Advanced Endometrial Cancer: PHAEDRA and DOMENICA

EP: 7.Adjuvant IO Strategies in Endometrial Cancer: RAINBO and GY020

EP: 8.Antibody Drug Conjugate Data in Endometrial Cancer: TROPiCS-03

EP: 9.Future Directions in the Management of Endometrial Cancer

Case 1:A 64-Year-Old Woman With Recurrence of Endometrial Cancer

August 2021

Initial Presentation

• A 64-year-old postmenopausal woman presented with abnormal uterine bleeding lasting 4 months

Patient History, Lifestyle and Clinical workup

• She notes that she underwent menopause at 55 years of age
• She is a widow, has no children, and lives alone
• PMH: arthritis, obesity (BMI=40), hypertension well controlled with medication
• ECOG PS=1

Initial Diagnosis and Treatment

• Endometrial biopsy results:
  • Endometrioid adenocarcinoma
  • Stage IA, Grade 1
  • IHC/Molecular testing results:
    • Mismatch repair deficiency (dMMR)
    • MSI-H
    • 3+ ER-positive
• The patient is counseled on surgical options and scheduled for surgery.

July 2022

Presentation at Recurrence

• Patient reports chronic pelvic pain over 4 weeks

Diagnosis of Recurrence

• CAP CT suggests relapsed/metastatic disease with involvement of 1 right external iliac lymph node

Treatment for Recurrence

• Carboplatin/paclitaxel (6x Q3W cycles) was administered.
• Chemotherapy was well tolerated, and a complete response was recorded at end of regimen.

February 2023

Diagnosis of Recurrence

• Disease relapse is documented on routine follow up.
• CT CAP shows heterogeneously enhancing mass in right suprarenal space, multiple bilateral pulmonary nodules, and a new right internal iliac lymph node (in addition to the previously observed positive lymph node)
• Fine needle aspirate of the suprarenal mass confirmed metastatic endometroid adenocarcinoma.
• The patient was counseled about systemic therapy options, during which she repeatedly expressed concerns about side effects.
• Dostarlimab was initiated with partial response noted on CT imaging 4 months after initiation

Transcript:

Ritu Salani, MD, MBA: The GARNET study was really informative. This was monotherapy dostarlimab in patients who had recurrent endometrial cancer after prior systemic therapy. Some of the implications for this study are that this shows that dostarlimab, particularly in the deficient mismatch repair protein group, had an excellent response of 44% in this population.

Dostarlimab was noted to have durable antitumor activity. It was also interesting to note that those patients with proficient mismatch repair endometrial cancer also had [approximately] a 14% response rate, which is probably pretty comparable to what we see with chemotherapy. All of this only received FDA approval in the mismatch repair deficient group.

In regard to the study design and efficacy, I think [the] GARNET study showed that there were comparable efficacy data to what we had standardly seen with monotherapy checkpoint inhibitors, and the design was well done [so] we didn’t see any new safety signals. I think this shows us that dostarlimab is a very viable option for patients with mismatch repair deficiency with recurrent endometrial cancer.

In the KEYNOTE-158 cohort of recurrent endometrial cancers: Once again, patients with deficient mismatched repair protein in endometrial cancer recurrence were treated with pembrolizumab monotherapy. Once again, we see that these patients had a 50% objective response rate. Once again, we see durable responses. The [adverse] effect profile was consistent with what we would expect with any immunotherapy agent. I think these, both GARNET and KEYNOTE-158, show that targeting mismatch repair deficiency with checkpoint inhibition is really a viable, successful option for these patients.

For patients with mismatched repair deficiency or MSI [microsatellite instability]-high and recurrent endometrial cancer, single-agent checkpoint inhibition is a really nice option for these patients, and patients can stay on therapy for quite some time. There are always…patients who do not respond and end up coming off therapy in a relatively short time frame due to progression of disease. A very small [number] of patients come off of therapy because of [adverse] effects or toxicities, but in my personal experience, which is limited because these drugs are still kind of evolving, we are seeing that these patients can have durable responses and can often stay on therapy for several years. It’s always interesting because sometimes we come into that debate of, “When do we stop therapy for these patients?” Even patients who’ve had complete response like to stay on therapy, so I think this is a new challenge. It’s a good problem about how long to continue these therapies, but these show that these therapies do have durable responses.

Transcript edited for clarity.