Tailored immunotherapy approach with Nivolumab in advanced transitional cell carcinoma

• Verfasst von: Grimm, Marc-Oliver [VerfasserIn]
• Verfasst von: Schmitz-Dräger, Bernd Jürgen [VerfasserIn]
• Verfasst von: Zimmermann, Uwe [VerfasserIn]
• Verfasst von: Grün, Barbara [VerfasserIn]
• Verfasst von: Baretton, Gustavo Bruno [VerfasserIn]
• Verfasst von: Schmitz, Marc [VerfasserIn]
• Verfasst von: Foller, Susan [VerfasserIn]
• Verfasst von: Leucht, Katharina [VerfasserIn]
• Verfasst von: Schostak, Martin [VerfasserIn]
• Verfasst von: Zengerling, Friedemann H. [VerfasserIn]
• Verfasst von: Schumacher, Ulrike [VerfasserIn]
• Verfasst von: Loidl, Wolfgang [VerfasserIn]
• Verfasst von: Meran, Johannes [VerfasserIn]
• Titel: Tailored immunotherapy approach with Nivolumab in advanced transitional cell carcinoma
• Verf.angabe: Marc-Oliver Grimm, Bernd Jürgen Schmitz-Dräger, Uwe Zimmermann, Christine Barbara Grün, Gustavo Bruno Baretton, Marc Schmitz, Susan Foller, Katharina Leucht, Martin Schostak, Friedemann Zengerling, Ulrike Schumacher, Wolfgang Loidl, and Johannes Meran
• E-Jahr: 2022
• Jahr: March 11, 2022
• Umfang: 10 S.
• Fussnoten: Gesehen am 03.08.2022
• Titel Quelle: Enthalten in: Journal of clinical oncology
• Ort Quelle: Alexandria, Va. : American Society of Clinical Oncology, 1983
• Jahr Quelle: 2022
• Band/Heft Quelle: 40(2022), 19, Seite 2128-2137
• ISSN Quelle: 1527-7755
• DOI: doi:10.1200/JCO.21.02631
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1813097216

Abstract

PURPOSE - - Several anti-programmed cell death (ligand)-1 (PD-[L]1) immune checkpoint inhibitors are approved in advanced/metastatic urothelial carcinoma (mUC). Recently, improved activity of an anti-PD-1/anticytotoxic T-cell lymphocyte-4 (CTLA-4) combination versus anti-PD-1 monotherapy has been reported. We report a response-based approach starting treatment with nivolumab monotherapy with nivolumab/ipilimumab as immunotherapeutic boost. - - METHODS - - After four doses of nivolumab induction, responders continued with nivolumab maintenance therapy. Patients with stable/progressive disease received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks for 2 doses followed by nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 2 doses, if not responding to the initial boost. Responders to boosts continued with nivolumab maintenance. Between July 2017 and April 2019, 86 patients were enrolled. The median follow-up is 7.7 months. The primary end point is objective response rate (ORR) per RECIST1.1. Secondary end points include efficacy of nivolumab induction, remission rate with nivolumab/ipilimumab boosts, overall survival, and safety. - - RESULTS - - Of all patients, 42, 39, and five were first- (1L), second- (2L), and third-line (3L), respectively. The median age was 68 years. The ORR with nivolumab monotherapy (assessed at week 8) was 29% in 1L and 23% in 2/3L, respectively. Forty-one patients received early (week 8) and 11 received later nivolumab/ipilimumab boosts. ORRs with nivolumab with or without nivolumab/ipilimumab (best overall response) were 45% and 27% in 1L and 2/3L, respectively. In 1L, 7 of 17 patients receiving boosts at week 8 improved, compared with 2 of 24 in 2/3L. - - CONCLUSION - - The tailored approach of TITAN-TCC shows meaningful clinical activity supporting dual checkpoint inhibition in 1L mUC. However, starting therapy with nivolumab exclusively appears inadequate given the aggressive nature of mUC. In 2/3L, nivolumab/ipilimumab boosts with escalating ipilimumab dose did not improve efficacy outcomes versus nivolumab monotherapy. An independent 2L cohort of TITAN-TCC receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 4 doses is ongoing.