Vimalanand Prabhu

Real-world treatment patterns and clinical outcomes in patients with advanced or recurrent endometrial cancer re-challenged with platinum-based chemotherapy in Europe

Although platinum re-challenge is a treatment option for patients with advanced/recurrent endometrial cancer, real-world outcomes for these patients in Europe are not well-documented. Thus, this study aimed to evaluate real-world treatment patterns and outcomes for platinum re-challenge in patients with advanced/recurrent endometrial cancer. Endometrial Cancer Health Outcomes-Europe (ECHO-EU) is a multi-center, retrospective, medical record review conducted in France, Germany, Italy, Spain, and the United Kingdom, evaluating treatment patterns and outcomes. Patients with advanced/recurrent endometrial cancer treated with first-line systemic therapy and experiencing disease progression between July 2016 and June 2019 were eligible for inclusion in ECHO-EU. This analysis used data from a subset of patients, the platinum re-challenge cohort, who received platinum-based chemotherapy as second-line therapy after previous adjuvant/neoadjuvant and/or first-line platinum therapy. Kaplan-Meier analyses since initiation of second-line therapy estimated real-world progression-free survival and overall survival. Of the 475 ECHO-EU patients, 70 patients (15%) were platinum re-challenged and had a median age of 67 years (range; 44-81). The platinum-free interval (PFI) was 6 months for 43 patients (61.4%). Complete or partial response to second-line therapy were achieved in 37.1% of patients, with similar overall response rates reported for patients with PFI 6 months, respectively. The median real-world progression-free survival from initiation of second-line therapy was 8.1 months (95% CI 7.6 to 10.0) overall and 7.6 (95% CI 5.3 to 19.8) and 8.5 (95% CI 7.9 to 12.0) months for patients with PFI <6 months and PFI ≥6 months, respectively. Patients with advanced/recurrent endometrial cancer who were re-challenged with a platinum-based therapy had similar outcomes, irrespective of their PFI, indicating that further research is needed to assess the value of PFI in endometrial cancer. The findings also suggest an unmet medical need and scope for novel treatments that may improve the overall survival for these patients.

Real-world perioperative treatment patterns and burden of recurrent disease in patients with high-risk endometrial cancer: a SEER-Medicare study

To elucidate unmet needs in high-risk endometrial cancer (EC), this study described perioperative treatment patterns in Medicare beneficiaries with high-risk EC and quantified the impact of disease recurrence on clinical and economic outcomes among patients receiving adjuvant therapy. Patients aged ≥66 years with high-risk EC (stage I/II EC of non-endometrioid histology or stage III/IVA EC of any histology) receiving hysterectomy with bilateral salpingo-oophorectomy from SEER-Medicare data (2007-2019) were identified; perioperative treatment patterns were described. Post-operative treatment patterns were described among patients receiving adjuvant therapy; overall survival (OS), all-cause and EC-related healthcare resource utilization and costs were evaluated from recurrence date (using a claims-based algorithm developed with clinical input) for recurrent patients and from a frequency-matched date for non-recurrent patients. Of 2,279 patients receiving EC surgery, 3.1% received neoadjuvant therapy and 55.3% received adjuvant therapy. Among 1,199 patients receiving adjuvant therapy, systemic adjuvant therapy with radiation (38.9%) was most common. Median OS was 1.4 years among 378 (31.5%) recurrent patients identified over a median follow-up of 3.7 years. Recurrent patients had significantly higher per-patient-year rates of all-cause outpatient visits (37.7 vs. 22.6), EC-related outpatient visits (14.5 vs. 3.0), and all-cause hospitalizations (1.3 vs. 0.4) than non-recurrent patients, and an excess of $84,562 and $62,128 in all-cause and EC-related annual costs, predominantly driven by hospitalizations. Our findings highlight the considerable clinical and economic burden experienced by patients with high-risk EC experiencing recurrence and emphasize the unmet need for novel therapies in early settings to mitigate this burden.

Real-world prevalence of microsatellite instability testing and related status in women with advanced endometrial cancer in Europe

Abstract Purpose To assess the real-world prevalence of microsatellite instability (MSI)/mismatch repair (MMR) testing and related tumor status in recurrent/advanced endometrial cancer patients in Europe. Methods Data were from two multi-center, retrospective patient chart review studies conducted in the United Kingdom, Germany, Italy, France and Spain: The Endometrial Cancer Health Outcomes-Europe-First-Line (ECHO-EU-1L) study and the ECHO-EU-Second-Line (ECHO-EU-2L) study. ECHO-EU-1L included recurrent/advanced endometrial cancer patients who received first-line systemic therapy between 1/JUN/2016 and 31/MAR/2020 after recurrent/advanced diagnosis. ECHO-EU-2L included patients with recurrent/advanced endometrial cancer who progressed between 1/JUN/2016 and 30/JUN/2019 following prior first-line systemic therapy. Data collected included patient demographics, MSI/MMR tumor testing and results, and clinical/treatment characteristics. Results ECHO-EU-1L included 242 first-line patients and ECHO-EU-2L included 475 s-line patients. For all patients, median age at recurrent/advanced diagnosis was 69 years, roughly half had endometrioid carcinoma histology and over 75% had Stage IIIB-IV disease at initial diagnosis. The prevalence of MSI/MMR testing in the first-line and second-line cohorts was similar (36.4 and 34.9%, respectively). Among those tested, a majority had non-MSI-high/MMR proficient tumors (80.7 and 74.7% among first- and second-line patients, respectively). About 15% had MSI-high/MMR deficient tumors in both cohorts, and a few patients had discordant results (3.4 and 10.8% among first- and second-line patients, respectively). Conclusion Prior to the approvals of biomarker-directed therapies for recurrent/advanced endometrial cancer patients in Europe, there were low MSI/MMR testing rates for these patients of just over one-third. Given the availability of biomarker-directed therapies, increased MSI/MMR testing may help inform treatment decisions for recurrent/advanced endometrial cancer patients in Europe.

Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy for treating previously treated advanced endometrial cancer in Sweden

Pembrolizumab plus lenvatinib was recently approved for the treatment of advanced or recurrent endometrial carcinoma in women with disease progression on or following prior treatment with a platinum‑containing therapy in any setting, and who are not candidates for curative surgery or radiation (KEYNOTE-775/Study-309; NCT03517449). The objective was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy from a Swedish healthcare perspective. A lifetime partitioned-survival model with three health states (progression free, progressed disease, death) was constructed. Chemotherapy was represented by paclitaxel or doxorubicin. Overall survival, progression-free survival, time on treatment, and utility data were obtained from KEYNOTE-775 (database lock: March 1, 2022). Costs (in 2020 Swedish Krona [SEK]) included drug acquisition and administration, health state, end of life, adverse event management, subsequent treatment, and societal (scenario analysis). Outcomes were calculated as quality-adjusted life-years (QALY) and life-years. Model results were presented as incremental cost-effectiveness ratios for all-comers, patients with proficient mismatch repair tumors, and deficient mismatch repair tumors. Deterministic and probabilistic sensitivity analyses were conducted. Pembrolizumab plus lenvatinib is a cost-effective treatment when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios of SEK 795,712 and 819,757 per QALY gained. Pembrolizumab plus lenvatinib was associated with a large incremental QALY and life-year gain per person versus chemotherapy over the model time horizon (1.49 and 1.76). Time-to-event data were incomplete and semiparametric and parametric curves were utilized for lifetime extrapolation. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the treatment's cost effectiveness in different countries. This partitioned survival analysis suggests that pembrolizumab plus lenvatinib is cost effective compared with chemotherapy in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. Results were robust to mismatch repair status and to changes in parameters/assumptions.

Real-World Utilization of Lenvatinib and Pembrolizumab Combination Therapy for the Treatment of Endometrial Cancer in the USA