RESUMO
BACKGROUND: Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score. PATIENTS AND METHODS: Patients with treatment-naïve aRCC received NIVO 240 mg every 2 weeks plus CABO 40 mg once daily or SUN 50 mg for 4 weeks (6-week cycles), until disease progression/unacceptable toxicity (maximum NIVO treatment, 2 years). Primary endpoint was progression-free survival (PFS) per blinded independent central review (BICR). Secondary endpoints were overall survival (OS), objective response rate (ORR) per BICR, and safety and tolerability. RESULTS: Overall, 323 patients were randomised to NIVO + CABO and 328 to SUN. Median PFS was improved with NIVO + CABO versus SUN [16.6 versus 8.4 months; hazard ratio (HR) 0.59; 95% confidence interval (CI) 0.49-0.71]; median OS favoured NIVO + CABO versus SUN (49.5 versus 35.5 months; HR 0.70; 95% CI 0.56-0.87). ORR (95% CI) was higher with NIVO + CABO versus SUN [56% (50% to 62%) versus 28% (23% to 33%)]; 13% versus 5% of patients achieved complete response, and median duration of response was 22.1 months versus 16.1 months, respectively. PFS and OS favoured NIVO + CABO over SUN across intermediate, poor and intermediate/poor IMDC risk subgroups; higher ORR and complete response rates were seen with NIVO + CABO versus SUN regardless of IMDC risk subgroup. Any-grade (grade ≥3) treatment-related adverse events occurred in 97% (67%) versus 93% (55%) of patients treated with NIVO + CABO versus SUN. CONCLUSIONS: After extended follow-up, NIVO + CABO maintained survival and response benefits; safety remained consistent with previous follow-ups. These results continue to support NIVO + CABO as a first-line treatment for aRCC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03141177.
Assuntos
Anilidas , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Renais , Neoplasias Renais , Nivolumabe , Piridinas , Sunitinibe , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Sunitinibe/uso terapêutico , Sunitinibe/farmacologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Masculino , Anilidas/uso terapêutico , Anilidas/farmacologia , Feminino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Nivolumabe/farmacologia , Piridinas/uso terapêutico , Piridinas/farmacologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Adulto , Seguimentos , Intervalo Livre de ProgressãoRESUMO
Objetivos: evaluar nivel de hemoglonina previo a quimioterapia (Qt.) en cáncer de ovario como factor pronóstico de tiempo libre de progresión a la primera línea. Materiales y métodos: se analizaron retrospectivamente 58 pacientes (ptes) del Instituto Oncológico de Córdoba. Se definió anemia como hemoglobina menor a 12 g/dl. Se tomaron 2 grupos, el primero con anemia previa a la Qt. versus el segundo sin anemia. Se obtuvieron curvas de tiempo libre de progresión (TLP) y de supervivencia global (SG) con Kaplan Meier. El análisis de variables con Chi cuadrado y test t de Student. Resultados: anemia pre Qt.: 32 (55%). Sin anemia: 26 (45%). Todas tratadas con platino. TLP medio de 15; SG en anemia: 28,4; sin anemia: 59,8 meses. No se encontró asociación entre Hb y estadio, enfermedad residual, CA 125 inicial y patrón de recaída. Un alto porcentaje de ptes. sin anemia (88,5%) realizaron más de 4 ciclos de Qt. comparado con las anémicas (66%-p=0,04). Se observó mayor porcentaje de respuesta completa (RC) en ptes. sin anemia 54% vs 22%. Ptes. con anemia presentaron 60% de progresión de enfermedad vs. 30% en ptes. con nivel mayor de 12. Existe asociación significativa entre Hb y respuesta a Qt. (p = 0,01). Los que han manifestado beneficio clínico, tienen en mayor proporción de Hb mayor a 12. Las anémicas tienen 4 veces más posibilidades de presentar progresión. Conclusión: las ptes. sin anemia tuvieron un TLP y SG más prolongado y una mejor respuesta que las ptes. con anemia estadísticamente significativa. Palabras claves: cáncer de ovario - anemia - recaída - factor pronóstico - hemoglobina.