Richard Woodman, MD Chief Clinical Officer, Oncology Business Group at Eisai, Inc.. In this video, he speaks about the ASCO 2022 Abstract – Efficacy of next line of therapy after treatment with lenvatinib (LEN) in combination with pembrolizumab (pembro) versus treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Exploratory analysis of Study 309/KEYNOTE-775 (309).
Origins:
In the multicenter, open-label, randomized, phase 3 Study 309/KEYNOTE-775, LEN + pembro demonstrated significant PFS and overall survival advantages, as well as a higher objective response rate compared to TPC in patients with aEC after systemic platinum-based treatment (Makker 2022, NEJM). These findings were observed in both all-comer patients and patients with DNA mismatch repair proficient (pMMR) illness. In this study, we looked at each arm’s PFS on next-line treatment (PFS2).
Methodology:
Patients with aEC and one prior platinum-based chemotherapy regimen (or up to two if one was given in a neoadjuvant/adjuvant context) were randomized (1:1) to LEN 20 mg orally QD + pembro 200 mg IV Q3W or TPC (doxorubicin at 60 mg/m2 IV Q3W or paclitaxel at 80 mg/m2 IV QW [3 weeks on; 1 week off]). MMR status (decided centrally) was used to stratify randomization; patients with pMMR tumors were further classified by Eastern Cooperative Oncology Group performance status, geographic location, and history of pelvic radiotherapy. PFS2 (defined as the time from randomization to illness progression on next line of treatment or death, whichever came first) was evaluated by investigator assessment in the pMMR and all-comer populations in this prespecified exploratory analysis.
Outcomes:
827 Pts (pMMR, n=697; dMMR, n=130) were randomly assigned to LEN + pembro (n=411) or TPC (n=416). At the data cutoff date (October 26, 2020), 567 patients (LEN + pembro, n=282; TPC, n=285) had discontinued study treatment, and 315 patients (LEN + pembro, n=115; TPC, n=200) had received subsequent systemic anticancer therapy (Table), most commonly doxorubicin (n=58) in the LEN + pembro arm and paclitaxel (n=57) in the In the pMMR group (14.4 vs 9.8 mo; HR 0.62, 95 percent CI 0.50–0.75) and the all-comer population (16.0 vs 9.5 mo; HR 0.56, 95 percent CI 0.46–0.67), median PFS2 was longer in the LEN + pembro arm compared to the TPC arm. Furthermore, the PFS2 rate at 6 months supported LEN + pembro over TPC in both the pMMR and all-comer populations (82.0 percent vs 74.8 percent) (81.7 percent vs 72.5 percent ).
Findings:
In pMMR and all-comer patients, the LEN + pembro group showed clinically significant improvements in PFS2 as compared to TPC. NCT03517449 is the clinical trial number.