Patient-Focused Approaches Are Key in Advanced Endometrial Cancer Treatment

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The complexities of treatment decisions and management strategies of advanced endometrial cancer may revolve around several factors including patient preference, prior treatment tolerance, and comorbidities, among others, experts discussed.

During a Community Case Forum on the evolution of immunotherapy for advanced endometrial cancer, Diana B. Czel, APRN, CNP, nurse practitioner Minnesota Oncology in Edina, Minnesota, and participants at the event discussed the importance of a multidisciplinary approach to managing adverse events, highlighting the importance of collaborative care and specialized interventions. Moreover, the dynamic nature of immune-related adverse effects challenged conventional perceptions, prompting a reevaluation of risk timelines and patient education strategies.

Case Study

Czel introduced the case of a 64-year-old postmenopausal woman who presented in August 2021 with abnormal uterine bleeding for 4 months. Her past medical history includes 1 pregnancy but no delivery, arthritis, obesity (with a BMI of 40), well-controlled hypertension, and an ECOG performance status of 1.

She was scheduled for a total laparoscopic hysterectomy and a bilateral salpingo-oophorectomy with sentinel lymph node mapping and tissue specimen collection. This led to her receiving a diagnosis of stage 1A, grade 1 endometrial cancer, with molecular test results indicating mismatch repair deficiency, microsatellite instability high, and 3+ ER-positive disease.

In August 2022, during surveillance, the patient reports intermittent pelvic pain during the last 4 weeks. A CT scan showed that the patient had recurrent disease with involvement of a single right external iliac lymph node. She is treated with systemic therapy, consisting of carboplatin and paclitaxel for 6 cycles every 3 weeks, “which is standard of care for first-line [treatment] for endometrial [cancer],” Czel said. The patient had a complete and durable response to treatment, and tolerated chemotherapy aside from occasional episodes of constipation that was addressed by hydration.

On routine follow-up in April 2023, a repeat CT shows disease progression involving retroperitoneal, multiple, bilateral pulmonary nodules. A fine-needle aspirate confirms metastatic endometroid adenocarcinoma. She was counseled on systemic therapy options, during which she expressed concerns about adverse effects.

Treatment Decisions

During the event, Czel discussed with participants factors that would influence the kind of treatment they would consider administering to this specific patient. Some of the responses included the tolerance of previous treatment and the length of time since the last treatment.

“Because she was less than 6 months [from her last treatment], using another platinum-based [chemotherapy] is not typically what you would want to see,” Czel noted. “But we could potentially go to Doxil (doxorubicin liposome), bevacizumab (Avastin), which [are] standard second-line [therapies]. That’s an option.”

After discussions with her care team, she decided on an immune checkpoint inhibitor monotherapy, specifically dostarlimab. The therapy was initiated with 4 doses at 21 days, and then she was followed up every 42 days after that.

“She just stayed on that indefinitely, so she was every 3 weeks for 4 [doses] and then continued indefinitely,” Czel said.

Several factors may play a role in treatment decision making, Czel and the participants discussed, including comorbidities, any autoimmune disorders, insurance reimbursement, the efficacy and tolerability of a therapy, and the distance a patient may have to travel to receive treatment.

“I think the other thing is sometimes, the insurance company wants you to do other [therapies] first before you go to the next step,” a participant said. “So [the insurance company] might say, ‘No, let’s go back to try this, and then you can go to that.’”

Another participant agreed, saying, “Insurance can be tough. I think all of these [factors] need to be in the forefront when you’re making a decision though.”

Treatment Duration and Adverse Effects

The participants also discussed how long patients can remain on immune checkpoint inhibitors. Czel noted that she has a patient who has been on the treatment for over 2 years, and a participant mentioned that she has seen a similar duration.

“I’ve had some patients who are comfortable after 2 years getting off [immune checkpoint inhibitors],” they said. “Others are a little bit nervous about getting off [the therapy] after 2 years.”

Four months after initiating dostarlimab, a follow-up CT indicated that the patient was having a partial response to the treatment. At cycle 9, she reported having fatigue, weakness, and a 10-pound weight gain.

“We know when we’re using our immunotherapies, we’ve got to start thinking, which –itis is this,” Czel said.

A diagnostic work-up helped the patient’s team discover that she had a high thyroid hormone level, which could explain the patient’s fatigue and weight gain. She was treated with levothyroxine while she remained on dostarlimab.

Some participants at the event noted that they sometimes manage the side effects amongst their team, or they refer a patient out to a specialist. For example, one participant mentioned that they get endocrinology involved for adverse events like adrenal sufficiency or hypophysitis. For other immune-related adverse events, participants mentioned having other areas involved like cardiology, pulmonology, and gastrointestinal specialists, when needed.

Czel discussed how immune-related adverse effects can occur almost any time within the duration of treatment.

“Some of these [adverse effects] are going to come in within the first few cycles or first few months,” she said. “And then…you have the same risk of having a thyroid event at 6 months vs 20 months. Whereas pneumonitis is going to be likely to show up later and have the highest incidence around [12 weeks] and then drop off the longer [a patient] is on it. This is an interesting thing because I thought the [immune-related adverse effect timing] were all the same, like the risk was the same for all of them. But I didn’t realize that you did have different risks at different times.”

One participant said that with different disease types, the timing of a patient’s risk for an adverse effect may vary.

Another participant agreed, saying, “I do feel like if someone’s going to get a rash though, it does show up earlier than most [adverse effects]. I feel like that’s one of the first to show up.”

Some other participants provided insights into their own experiences with immune-related adverse effects, like how rash can occur 2 to 3 months after treatment initiation, or most adverse effects can be observed within the 6- to 10-week time period.

“I think it's important for us to make sure that we're educating our patients, too, about [adverse effects],” Czel said. “[Tell patients,] ‘I'm glad nothing's happening now, but you’ve got to call me if you get short of breath. Let me know.’ And so, when we're looking at immunotherapy-related adverse events, we know that most of these are going to be treatment related.”