Safety, tolerability, and clinical activity of selinexor in combination with pembrolizumab in treatment of metastatic non–small cell lung cancer
Menée à partir de données portant sur 17 patients atteints d'un cancer du poumon non à petites cellules de stade métastatique (âge médian : 67,5 ans), cette étude prospective évalue l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression, et la toxicité du sélinexor en combinaison avec le pembrolizumab
Background: In lung cancer, overexpression of nuclear export proteins can result in inactivation of critical tumor suppressor proteins and cell-cycle regulators. Selective suppression of nuclear export proteins has immunomodulatory activities. Here, clinical safety and early efficacy data are presented on the combination of pembrolizumab and an oral selective nuclear export inhibitor, selinexor, for the treatment of metastatic non–small cell lung cancer (mNSCLC). Methods: The primary objective of this prospective investigator-initiated study was to determine the safety and tolerability of selinexor in combination with pembrolizumab in patients with mNSCLC. Secondary objectives included determination of objective tumor response rate, disease control rate, and progression-free survival duration. Results: A total of 17 patients were included in the final analysis. Fifteen (88%) received more than two lines of prior systemic therapy and 10 (59%) had prior exposure to anti–PD-1/programmed death-ligand 1 (PD-L1) therapy. The median age was 67.5 years. Ten patients had grade ≥3 adverse events related to selinexor treatment. Responses to treatment occurred in patients who did and did not undergo previous anti–PD-1/PD-L1 therapy and in patients with activating driver mutations. The median overall survival and progression-free survival were 11.4 months (95% CI, 3.4–19.8 months) and 3.0 months (95% CI, 1.7–5.7 months), respectively. The overall response rate was 18% and the 6-month disease control rate was 24%. Conclusions: Selinexor in combination with pembrolizumab demonstrated promising antitumor activity in patients with mNSCLC, including those who had previously received anti–PD-1/PD-L1 therapy. The therapy-related toxic effects were consistent with the prior safety data for both drugs, and no overlapping toxic effects were observed.
Cancer 2022