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Tailored Immunotherapy Approach With Nivolumab in Advanced Transitional Cell Carcinoma.
Grimm, Marc-Oliver; Schmitz-Dräger, Bernd Jürgen; Zimmermann, Uwe; Grün, Christine Barbara; Baretton, Gustavo Bruno; Schmitz, Marc; Foller, Susan; Leucht, Katharina; Schostak, Martin; Zengerling, Friedemann; Schumacher, Ulrike; Loidl, Wolfgang; Meran, Johannes.
Afiliação
  • Grimm MO; Department of Urology, Jena University Hospital, Jena, Germany.
  • Schmitz-Dräger BJ; Urologie 24, St Theresien Hospital, Nuremberg, Germany.
  • Zimmermann U; Department of Urology and Pediatric Urology, University Hospital Erlangen, Erlangen, Germany.
  • Grün CB; Department of Urology, Greifswald University Hospital, Greifswald, Germany.
  • Baretton GB; Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
  • Schmitz M; Institute of Pathology, University Hospital Carl Gustav Carus, Dresden, Technical University, Dresden, Germany.
  • Foller S; National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.
  • Leucht K; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Schostak M; National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.
  • Zengerling F; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Schumacher U; Department of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
  • Loidl W; Department of Urology, Jena University Hospital, Jena, Germany.
  • Meran J; Department of Urology, Jena University Hospital, Jena, Germany.
J Clin Oncol ; 40(19): 2128-2137, 2022 07 01.
Article em En | MEDLINE | ID: mdl-35275706
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Carcinoma de Células de Transição Limite: Aged / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Carcinoma de Células de Transição Limite: Aged / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article