Pembrolizumab–lenvatinib beyond immunotherapy progression in endometrial cancer: A real-world analysis.
Abstract
5612 Background: The integration of immune checkpoint inhibitors (ICIs) into frontline therapy for advanced or recurrent endometrial cancer (aEC) has transformed treatment paradigms. However, the management of patients who experience disease progression after ICI-based therapy remains challenging. In the absence of prospective guidance, ICI rechallenge and ICI-based combinations beyond progression are already being used in clinical practice. In this real- world study, we aimed to evaluate the effectiveness of pembrolizumab-lenvatinib (PL) beyond ICI progression in patients with aEC. Methods: A retrospective study was conducted using the TriNetX database, defining two cohorts of aEC patients: 527 patients who received PL and 2,582 patients who did not receive PL but were treated with either paclitaxel or doxorubicin (chemotherapy, CHT cohort). Both cohorts had received an ICI-based regimen within the previous three years. Patients with any other malignancy were excluded. Propensity score matching (PSM) was used to balance cohorts for age, race, body mass index (BMI), major comorbidities, mismatch repair (MMR) status and prior olaparib exposure. The primary endpoint was overall survival (OS); secondary endpoints were treatment-related toxicities, including hypothyroidism and heart failure. OS was estimated using Kaplan–Meier methods, with hazard ratio (HR) used to compare OS and odds ratio (OR) used to compare toxicities. Results: After PSM, 521 matched pairs of patients (mean age +/- standard deviation: 66,4 +/- 9,6 years) were included in the PL and CHT cohorts, respectively, with well-balanced baseline characteristics. Asian patients were similarly represented in the two groups (7.3% vs 7.4%), most patients were obese (BMI ≥30: 59,3% vs 57,8%), only a small proportion had known MMR-deficient disease (2.1% and 1.9%), and just few of them were previously treated with olaparib (1.9%). After a median follow-up of 8.6 months (interquartile range, IQR 14.3) in the PL cohort and 11.5 months (IQR 16.7) in the CHT cohort; median OS was 27,4 months with PL and was not reached with CHT (HR = 2.25, 95% CI 1.76–2.89; p<0.001). Conclusions: The rise of ICIs in frontline therapy for aEC marks a paradigm shift and raises the question on how to manage patients who progress after prior immunotherapy. This is the first large, real-world cohort analysis to evaluate PL beyond immunotherapy progression in aEC. In this study, PL did not improve OS compared with CHT in patients previously exposed to ICIs. These findings suggest that PL may not be the optimal choice in this setting, and further work is needed to clarify the best post-ICI sequencing strategies and to develop approaches to overcome resistance.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Alberto Farolfi
IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy
Chiara Casadei
Emanuela Scarpi
Milena Urbini, PhD, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Thomas F. Eleveld, PhD, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Maurizio Polano, PhD, Experimental and Clinical Pharmacology Unit, IRCCS Centro di Riferimento Oncologico di Aviano (CRO), Aviano, Italy; Emanuela Scarpi, PhD, Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Cecilia Menna, MD, and Caterina Gianni, MD, Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Ferdinand W. Janssen, MSc, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Giuseppe Schepisi, MD, Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Giorgia Gurioli, PhD, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei ...
Eleonora Paoletti
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Francesca Rusconi
TriNetX Europe, Milan, Italy
Simone Sabbioni
IRCCS Istituto Romagnolo per lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Caterina Gianni
Milena Urbini, PhD, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Thomas F. Eleveld, PhD, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Maurizio Polano, PhD, Experimental and Clinical Pharmacology Unit, IRCCS Centro di Riferimento Oncologico di Aviano (CRO), Aviano, Italy; Emanuela Scarpi, PhD, Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Cecilia Menna, MD, and Caterina Gianni, MD, Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Ferdinand W. Janssen, MSc, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Giuseppe Schepisi, MD, Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Giorgia Gurioli, PhD, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei ...
Michela Palleschi
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Daniela Montanari
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Andrea Carlini
IRCCS Istituto Romagnolo per lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Giulia Miserocchi
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Nicola Gentili
9Instituto Romagnolo per lo Studio dei Tumori, Meldola, Italy
Olga Serra
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Giandomenico Di Menna
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Alice Andalò
9Instituto Romagnolo per lo Studio dei Tumori, Meldola, Italy
Filippo Merloni
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Marianna Sirico
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Lorenzo Cecconetto
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
Samanta Sarti
IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy
Antonino Musolino
IRCCS Istituto Romagnolo per lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy