Optimizing subsequent therapy in AEC/REC patients between ICI and PCC with duration of PFI in mind

22 Sep 2023

Researchers from the Department of Gynecology and Obstetrics, Kyushu University Hospital conducted a single-center, retrospective study to assess the efficacy of platinum-containing chemotherapy (PCC) as a second/third-line treatment for patients with advanced or recurrent endometrial cancer (AEC/REC).1 It was reported that patients who received first-line PCC and had a platinum-free interval (PFI) of ≥6 months displayed favorable responses under second/third-line PCC.1  

Globally, endometrial cancer (EC) is the seventh most prevalent cancer in women, primarily affecting elderly women between the ages of 65 and 75.2 For AEC/REC patients, the prognosis remains dismal with a 5-year overall survival (OS) ranging between 20% to 25%.2 The 2022 European Society for Medical Oncology (ESMO) guidelines recommend carboplatin-paclitaxel as the first-line treatment in patients with EC, but recommendations on second/third line treatment options were varied with different strength and level of ecvidence.2  

The clinical efficacy of pembrolizumab-lenvatinib, an immune checkpoint inhibitor (ICI) combination, as a second-line treatment for AEC/REC was first reported in KEYNOTE-775, achieving significantly better survival outcomes against cytotoxic monotherapy for patients with AEC.3 However, cytotoxic monotherapy is rarely the practice of PCC management, thus the evidence that ICIs offered a more competent option over combination PCC regimens for second/third-line treatment of AEC/REC required further justification.1 Hence, a study was conducted to compare the efficacy of PCC as second/third-line treatment for patients with AEC/REC against the results of KEYNOTE-775.1

This retrospective study analyzed patient data between 2005 and 2020 collected from a Japanese hospital.1 The study included 65 patients with AEC/REC who were treated with PCC as second/third-line treatment, upon which 54% (n=30) of patients were categorized into the platinum-sensitive subgroup due to having a PFI of ≥6 months.1 Patients with <6 months of PFI (n=35) were labeled as platinum-refractory instead.1 Typical PCC regimens consisting of paclitaxel-carboplatin, adriamycin-cisplatin, or docetaxel-carboplatin were administered to patients once every 3 to 4 weeks.1 The ORR, PFS and OS of the two patient groups were assessed as study endpoints.1

In general, the treatment outcomes of PCC for the platinum-sensitive group were more pronounced than those of the platinum-refractory group.1 Results obtained from this analysis revealed that the use of second/third-line PCC contributed to significant survival benefits in the platinum-sensitive group, inducing a significantly longer median PFS (9.5 vs. 3.0 months; p<0.001), and OS (53.0 vs. 10.0 months; p<0.0001) compared to the platinum-refractory group.1 In addition, the platinum-sensitive group exhibited a superior ORR (43.3% vs. 11.4%).1 Further multivariate analysis identified PFI as a significant prognostic factor for PFS and OS benefits of AEC/REC patients under PCC (p<0.0001).1  

The data from this retrospective study was then compared with the results of KEYNOTE-775, which reported an overall response rate (ORR) of 31.9%, a median progressive-free survival (PFS) of 7.2 months, and a median overall survival (OS) of 18.3 months for patients on pembrolizumab and levatinib.3 Patients with a PFI ≥6 months had comparable clinical efficacy with pembrolizumab-lenvatinib in KEYNOTE-775.1 However, for patients with a PFI of <6 months, ICI therapy such as pembrolizumab-lenvatinib offers a considerably larger benefit, and would be the preferable treatment choice.1

  1. Yasunaga M, et al. Decision-making for Subsequent Therapy for Patients With Recurrent or Advanced Endometrial Cancer Based on the Platinum-free Interval. Am J Clin Oncol. 2023;46(9):387-391.
  2. Oaknin A, et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(9):860-877.
  3. Makker V, et al. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022;386(5):437-448.