Key Takeaways
- Despite ongoing studies to determine the best treatment protocols for recurrent or advanced endometrial cancer, there is currently insufficient data to determine the optimal combination of drug and irradiation therapy. In the absence of standard protocols, treatment decisions should address the most pressing issues — either localized control or peritoneal spread — and be determined by parametrial margin.
- Some promising new treatments are more costly than chemotherapy, warranting a re-evaluation of the Institute for Clinical and Economic Review’s incremental cost-effectiveness ratio (ICER) standard of $100k/Quality Adjusted Life Year (QALY).
- Moving forward, liquid biopsies and next-generation sequencing (NGS) can help patients receive more effective, targeted treatments at an earlier disease stage. Currently, however, the diagnostic efficacy of these measures is not sufficiently validated, so they are not yet ready to be incorporated into clinical practice.
From March 25 to March 28, 2023, women’s health care professionals from around the world gathered in Tampa, Florida, for the Society of Gynecologic Oncology’s (SGO) 2023 Annual Meeting on Women’s Cancer. This year’s meeting included more than 50 live and live-streamed sessions and more than 100 posters and e-posters covering topics such as treatment options for recurrent and advanced endometrial cancer.
Stephanie V. Blank, MD, is the director of gynecologic oncology for the Mount Sinai Health System and professor of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York City. Her clinical focuses include treating ovarian, uterine, and cervical cancer and caring for women with an increased genetic risk for cancer. In this article, Dr Blank shares her insights into the most recent research on advanced and recurrent endometrial cancer presented at the 2023 SGO Annual Meeting.
Results presented from the randomized phase III Lunchbox trial revealed there was no difference observed between cisplatin and irradiation followed by carboplatin and paclitaxel vs carboplatin and paclitaxel followed by irradiation then carboplatin and paclitaxel in terms of progression-free survival, overall survival, or adverse events.1 How will these findings impact the determination of the optimal adjuvant treatment strategy for patients with advanced endometrial cancer? What follow-up studies might you wish to see?
Now that we have the long-term survival results of GOG 258 (ClinicalTrials.gov identifier: NCT00942357) not showing a survival benefit of adding radiation therapy (RT) to chemotherapy for advanced endometrial cancer,2 this answer may be irrelevant, but prior to knowing that, I would have said that decision should be based on uterine and clinical factors. We must consider what we should be most immediately worried about: local control or peritoneal spread? If you have positive parametrial margin, start with cisplatin and RT. If you have serous cancer, start with chemotherapy.
Treating patients with recurrent advanced endometrial cancer who have failed platinum-based therapy with a combination of lenvatinib and pembrolizumab results in more patients staying alive at the 2-year mark than with chemotherapy treatment, yet the cost of the combination therapy is too high for most patient’s willingness-to-pay threshold.3 What strategies could a clinician employ to promote the more effective treatment option?
The Institute for Clinical and Economic Review’s ICER was set at $100k/QALY in 1982 and needs to be re-examined — we have changed expectations regarding survival, and we should also change our expectations regarding willingness to pay. Adjusting for inflation, $164k/QALY might not be too high for the willingness-to-pay threshold. While this treatment will not be more cost-effective than chemotherapy, it will improve survival and is worthy of consideration with an eye to update ICER values.
Patients with advanced and high-grade endometrial cancers with surgically unresectable nodal involvement who undergo neoadjuvant chemoradiation (NACRT) prior to surgical staging do not display a clearly correlated survival benefit when receiving adjuvant chemotherapy (ACT). There did appear to be a possible trend toward improved survival with ACT for patients with endometrioid histology and macroscopic residual disease.4 Given these results, what factors must a clinician consider before recommending ACT for a patient during NACRT treatment?
Likely, there will be patient factors such as frailty and tolerance to the neoadjuvant treatment and surgery, as well as tumor factors such as presence of residual tumor (how much and how symptomatic), so I suspect the decision would be made postoperatively.
In general, have you seen improved quality-of-life outcomes in patients receiving preoperative neoadjuvant radiation therapy in this population? Which patients tend to benefit from this?
This is all extrapolated from ovarian cancer data. To my knowledge, we do not have prospective data here.I would generally give neoadjuvant chemotherapy (or maybe a chemo-checkpoint inhibitor). If I eventually plan on operating, I would avoid RT. The only time I would use NACRT would be to control very significant bleeding.
Measuring tumor fraction via liquid biopsy in advanced endometrial carcinoma may serve as a prognostic biomarker, with 1 study finding that pretreatment circulating tumor DNA (ctDNA) was correlated with baseline tissue biopsy.5 Is there a case to be made for incorporating liquid biopsies for this population outside of a clinical trial setting? Why or why not?
This is a very attractive possibility, but it is really too soon to incorporate this practice into a general clinical setting until it is further validated. The positive aspect of this practice is that establishing a biomarker to predict response could spare patients from the toxicity of treatments that are not working and could get them onto other treatments that are more likely to work, but the negative aspect is that this approach is not currently validated. Right now, I believe the negatives outweigh the positives, so I would not make clinical decisions based on liquid biopsy at this time.
New evidence revealed that NGS for human epidermal growth factor receptor 2 (HER2) identified an additional 11% of patients with HER2-positive tumors that were not identified by clinical HER2 testing, increasing eligibility for targeted therapy for patients with advanced and recurrent endometrial cancers.6 The presenters of 1 study argued that clinicians should add NGS testing without abandoning clinical HER2 testing. What is the advantage of conducting both forms of tests, and are there any downsides?
The downside of additional testing is the cost. We do not know whether NGS HER2 is indicative of response to HER2-directed treatment, as NGS was not used to identify patients in the studies that demonstrated effectiveness of HER2-directed therapy. Logically, it should, but we do not know as yet, so the added cost burden may not be justifiable.
This Q&A was edited for clarity and length.
References
1. Barlin JN, Mahar B, Ata A, et al. Lunchbox trial: a randomized phase III trial of cisplatin and irradiation followed by carboplatin and paclitaxel vs. sandwich therapy of carboplatin and paclitaxel followed by irradiation then carboplatin and paclitaxel for advanced endometrial carcinoma. Poster presented at: Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL.
2. Matei D, Filiaci V, Randall ME, et al. Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med. 2019;380(24):2317-2326. doi:10.1056/NEJMoa1813181
3. Dioun S, Diggs A, Chen L, et al. Cost-effectiveness of lenvatinib plus pembrolizumab versus chemotherapy for recurrent mismatch repair-proficient endometrial cancer after platinum-based therapy. Poster presented at: Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL.
4. Flanigan MR, Ertel M, Vargo JA, et al. The role of adjuvant chemotherapy in endometrial cancer following pre-operative neoadjuvant chemoradiation therapy. Poster presented at: Society of Gynecologic Oncology(SGO) 2023 Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL.
5. Soliman PT, Yang RK, Fellman BM, et al. Exploring the utility of liquid biopsy (ctDNA) as a translational endpoint in clinical trials for endometrial cancer. Abstract presented at: Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL.
6. Lee SS, Allen K, Espino K, et al. Next-generation sequencing complements conventional clinical HER2 testing for advanced or recurrent endometrial tumors. Poster presented at: Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL.
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Reviewed April 2023
