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A U.S. Food and Drug Administration-pooled Analysis of Frontline Combination Treatment Survival Benefits by Risk Groups in Metastatic Renal Cell Carcinoma.
Lee, Daniel; Gittleman, Haley; Weinstock, Chana; Suzman, Daniel; Bloomquist, Erik; Agrawal, Sundeep; Brave, Michael; Brewer, Jamie; Fallah, Jaleh; Singh, Harpreet; Tang, Shenghui; Ibrahim, Amna; Pazdur, Richard; Beaver, Julia A; Amiri-Kordestani, Laleh.
Afiliação
  • Lee D; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA. Electronic address: daniel.lee@fda.hhs.gov.
  • Gittleman H; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Weinstock C; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Suzman D; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Bloomquist E; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Agrawal S; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Brave M; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Brewer J; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Fallah J; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Singh H; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Tang S; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Ibrahim A; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Pazdur R; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Beaver JA; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  • Amiri-Kordestani L; Center for Drug Evaluation and Research, Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Eur Urol ; 84(4): 373-378, 2023 10.
Article em En | MEDLINE | ID: mdl-37271635
ABSTRACT

BACKGROUND:

While frontline immuno-oncology/tyrosine kinase inhibitor (IO/TKI) combination therapy has established a benefit in metastatic renal cell carcinoma (mRCC), this may differ by International Metastatic RCC Database Consortium (IMDC) risk grouping. Looking at individual trials, we noted an apparently smaller magnitude of benefit for favorable-risk disease.

OBJECTIVE:

We aimed to assess treatment benefit by risk groupings, especially in favorable-risk, augmenting patient numbers via a pooled analysis. DESIGN, SETTING, AND

PARTICIPANTS:

We pooled four frontline mRCC trials of IO/TKI combinations including 3,098 patients (839 favorable-risk) with approvals from 2019 to 2021. INTERVENTION All trials used IO/TKI combinations as the treatment option and sunitinib as the control. OUTCOME MEASUREMENTS AND STATISTICAL

ANALYSIS:

We analyzed progression-free survival (PFS) and overall survival (OS) by IMDC groupings. To specifically address the favorable-risk group, we combined all others into an intermediate/poor-risk group. RESULTS AND

LIMITATIONS:

In this exploratory analysis adjusted for baseline covariates, IO/TKI combinations have yet to demonstrate an OS benefit in favorable-risk (hazard ratio [HR] 1.24; 95% confidence interval [CI] 0.86, 1.78) despite demonstrating an OS benefit in the intermediate/poor-risk group (HR 0.64; 95% CI 0.55, 0.75). In contrast, IO/TKI demonstrated a PFS benefit for both the favorable-risk (HR 0.63; 95% CI 0.50, 0.79) and the intermediate/poor-risk (HR 0.52; 95% CI 0.45, 0.60) group. For objective response rate, a smaller difference was observed between the combination and sunitinib arms in favorable-risk (68.2% vs 49.9%) versus intermediate/poor-risk (59.9% vs 36.5%) groups, while the difference in complete response rate was larger for favorable-risk (15.3% vs 6.0%) versus intermediate/poor-risk (9.1% vs 3.4%) groups.

CONCLUSIONS:

The frontline IO/TKI combination therapy benefit was shown to be greater in the intermediate/poor-risk group than in the favorable-risk group. The OS benefit observed with IO/TKI for mRCC has yet to be demonstrated for favorable-risk patients; longer follow-up is needed. PATIENT

SUMMARY:

Patients with intermediate/poor-risk metastatic renal cell carcinoma derive an overall survival benefit from immuno-oncology/tyrosine kinase inhibitor combinations, while data for favorable-risk remain immature.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / Neoplasias Renais / Antineoplásicos Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Humans País como assunto: America do norte Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Renais / Neoplasias Renais / Antineoplásicos Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Humans País como assunto: America do norte Idioma: En Ano de publicação: 2023 Tipo de documento: Article