A 64-Year-Old Woman With Advanced Endometrial Carcinoma - Episode 5

Treating Advanced Endometrial Carcinoma: Counseling on Safety Profiles

Recommendations on how to best prepare patients for chemotherapy, lenvatinib plus pembrolizumab, and other therapies used to treat advanced endometrial cancer.

Robert L. Coleman, MD, FACOG, FACS: Adverse events are very important to consider when choosing a regimen. Every counseling session that I go through with a patient, when we’re going to start a new therapy or are already on therapy, we review those adverse events so that they’re clear and known to the patient for their expectations. One of the most important reasons to do this, other than to provide a thorough counseling for the patient, is that it allows us to navigate through events that might discontinue treatment. As you could imagine, patients who are off therapy aren’t likely to benefit. We try to provide the expectation for these so that it can be navigated in an effort to keep patients on treatment.

Most of us are very familiar with chemotherapy. Paclitaxel-carboplatin as a chemotherapy regimen is a day in and day out therapy, and the others that we’ve used, like doxorubicin, have been around for decades. Our experience with those drugs with respect to the hematologic and nonhematologic toxicities are very front of mind. For clinicians who haven’t treated a lot of patients with endometrial cancer with combination chemotherapy, there are some additional considerations. In general, these patients are older and more frail. They may also have comorbidities, which may make the routine administration of these drugs more challenging. Those need to be taken into consideration.

Also, many of our patients with endometrial cancer have pelvic radiation. This patient received cuff radiation, which doesn’t impact the marrow much. However, pelvic radiation, and pelvic radiation with paraaortic radiation, can provide a very large barrier to the administration of intended doses and the tolerance of chemotherapy over time. This is one of those areas where breaks, dose reductions, and modifications may be necessary with chemotherapy.

With respect to the other options, lenvatinib and pembrolizumab both have a long track record within the clinical community. Pembrolizumab is approved in a number of different tumors and generally has a very predictable adverse effect profile. When combined with lenvatinib, especially at the doses that we use—20 mg of lenvatinib and 200 mg of pembrolizumab—we see some toxicities that are factors that wouldn’t be in our normal evaluation of women who are on endometrial cancer recurrence therapies because we don’t use a lot of bevacizumab here.

Lenvatinib can cause hypertension, which can be difficult treat at times. It’s something that we can identify early and is one of the factors that we’d want to educate the patient on and intervene early so that we can maintain the combination. This is an adverse effect that needs attention. And although it’s not uncommon to do a dose reduction in the presence of this, if we have trouble getting control, fortunately the frequency of patients discontinuing therapy for hypertension is relatively modest. Our strategies for dose interruption and dose reduction have been effective in maintaining persistence of this.

The combination of the 2 drugs leads to a higher rate of overall toxicities, but fortunately we didn’t necessarily see an overlap. But the 2 drugs given at their recommended doses definitely have these particular features, and we see general effects that we see with therapy, like fatigue, nausea, vomiting, and diarrhea, and also immune adverse effects, such as hyperthyroidism, stomatitis, and rash. These types of features aren’t uncommonly seen with the drug and were seen in the regimens as a combination as well.

Transcript edited for clarity.

Initial Presentation

  • A 64-year-old postmenopausal woman presented with abnormal uterine bleeding for about 2 months. She has two grown children, underwent menopause at 57 years of age, has no known family history of cancer.
  • PMH: BMI is 32, and she has hypertension that is controlled with medication
  • PE: Notable for large uterus and right lower quadrant abdominal tenderness on palpation

Clinical work-up

  • Endometrial biopsy: endometrioid adenocarcinoma, FIGO grade 1
  • Surgery: ELAP TAH BSO with bilateral pelvic node dissection
  • Pathology: grade 2 endometrioid adenocarcinoma, 18 negative pelvic nodes, invasive 2.1 cm of 2.3 cm myometrium
  • Molecular testing shows MSS, MMR proficient, and HER2-

Treatment

  • Postoperative radiotherapy: vaginal cuff brachytherapy to a dose of 21 Gy in 3 fractions
  • 14 months after completing radiotherapy, she presented with new RLE edema and right hydroureter
  • She then was treated with carboplatin/paclitaxel chemotherapy which was well tolerated
  • Nine months later the patient has disease relapse with metastases to the paraaortic lymph nodes and lung
  • She is now treated with lenvatinib/pembrolizumab