First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update.

BACKGROUND: To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. PATIENTS AND METHODS: Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. RESULTS: With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. CONCLUSIONS: With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.

La anemia como factor pronóstico de recaída en cáncer de ovario / The anemia like factor prognosis of relapse in ovary cancer

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.

Cost-effectiveness of new targeted therapy sunitinib malate as second line treatment in metastatic renal cell carcinoma in Argentina

Objetivo: el objetivo del estudio fue estimar el costo-efectividad del malato de sunitinib versus el mejor cuidado paliativo (best supportive care BSC) en el tratamiento de carcinoma de células renales metastásico resistente a citoquinas (mRCC) en pacientes que fallaron a interleuquina 2 (IL-2), interferón alfa o una combinación de ambos. Métodos: se desarrollo un modelo de Markov y se adaptó a las circunstancias argentinas. Los resultados de efectividad fueron tomados de estudios clínicos y de la base de datos de US Medicare. Los datos fueron ajustados con las estimaciones de mortalidad general de la población tomadas de fuentes argentinas. Las utilidades fueron colectadas con la ayuda del cuestionario EQ-5D en el estudio clínico. La principal fuente de datos de uso de recursos y costos fueron tomados de un instituto oncológico de Argentina. Los costos fueron calculados en pesos argentinos (AR$) de 2006. Tanto los costos como la efectividad fueron descontados a una tasa anual de 3%. El costo-efectividad incremental fue calculado por mes libre de progresión (PFM), año de vida ganado (YLG) y año de vida ajustado por calidad (QALY). Se efectuó un análisis de sensibilidad determinístico y probabilístico para las variables de efectividad y costo.

Introduction: The objective of this study was to estimate the cost-effectiveness of sunitinib malate versus the best palliative care (BSC best supportive care) in the treatment of metastatic renal cell carcinoma resistant to cytokines (MRCC) in patients who failed to interleukin 2 ( IL-2), interferon alpha or a combination of both. Methods: We developed a Markov model and was adapted to the circumstances in Argentina. The results of effectiveness were obtained from clinical studies and the database of U.S. Medicare. The data were adjusted by the estimates of mortality of the population taken from Argentine sources. The utilities were collected with the help of the EQ-5D questionnaire in the clinical study. The main source of data for resource use and costs were taken from an oncology institute in Argentina. The costs were calculated in Argentine pesos (AR $), 2006. Both the costs and effectiveness were discounted at an annual rate of 3%. The cost-effectiveness was estimated by progression-free months (PFM), year of life gained (YLG) and years of life adjusted for quality (QALY). An analysis of deterministic and probabilistic sensitivity for the variables of cost and effectiveness.

A randomised phase II study of oxaliplatin alone versus oxaliplatin combined with 5-fluorouracil and folinic acid (Mayo Clinic regimen) in previously untreated metastatic colorectal cancer patients.

The aim of this study was to examine the efficacy and safety of both oxaliplatin as a single agent and oxaliplatin in combination with dailyx5 bolus 5-fluorouracil and folinic acid (5-FU/FA, Mayo clinic regimen) in the first-line treatment of metastatic colorectal cancer (CRC) patients. 73 advanced CRC patients were randomised to receive either oxaliplatin 85 mg/m(2) every 2 weeks (35 patients), or the same treatment combined with 5-FU 425 mg/m(2)/day and FA 20 mg/m(2)/dayx5 days every 4 weeks (38 patients). Treatment was continued until disease progression or unacceptable toxicity. All patients had documented inoperable disease and no previous chemotherapy for advanced disease. Based on the investigators' assessment of best response, objective response rate was 9% (95% confidence interval (CI) 2-24%) in the oxaliplatin arm, and 45% (95% CI 27-64%) in the oxaliplatin+5-FU/FA arm. Median progression-free survival (PFS) was 2 months (95% CI 1.7-2.4 months) in the oxaliplatin arm and 3.9 months (95% CI 2.9-5 months) in the oxaliplatin+5-FU/FA arm. Severe neutropenia was seen in 23% of patients in the oxaliplatin+5-FU/FA arm, and none in the oxaliplatin arm. There were two treatment-related deaths, both in the oxaliplatin+5-FU/FA arm. In the oxaliplatin+5-FU/FA arm, severe diarrhoea, vomiting and stomatitis were seen in 34, 14 and 14% of the patients, respectively. In conclusion, oxaliplatin at a dose of 85 mg/m(2) given every 2 weeks was well tolerated and has limited activity in metastatic CRC, while the combination of this treatment with the full-dose Mayo clinic regimen (5-FU bolus 425 mg/m(2)/day+FA 20 mg/m(2)/dayx5 days every 4 weeks), although active, was unfeasible due to a high level of myelosuppression and gastrointestinal toxicity. Alternative lower dosing or other regimens are to be explored to ascertain the value of bolus 5-FU/FA combined with oxaliplatin.

Uracil/tegafur plus oral calcium folinate in advanced breast cancer.

Uracil and tegafur (in a molar ratio of 4:1 [UFT]) has proven activity against breast cancer and is delivered in an easy-to-administer oral formulation. Orzel, which combines UFT with the oral biomodulator, calcium folinate, may provide even greater antitumor efficacy against breast cancer. Here, we describe the preliminary results of this phase II trial investigating the feasibility of 250 mg/m2/day of UFT plus 45 mg/day of oral calcium folinate administered to highly pretreated patients with advanced breast cancer. The results indicate a highly tolerable regimen and an overall response rate of 27.8% in a group of poor-prognosis patients. These findings warrant continued investigation.

[Phase II trial with navelbine + cisplatin + etoposide in the treatment of inoperable non-small cell lung carcinoma]. / Estudio en fase II de navelbine + cisplatino + etoposido en el tratamiento del cáncer de pulmón no células pequeñas inoperable.

40 patients with advanced non-small cell lung cancer not previously treated were included in a study at phase II with vinorelbine 20 mg/Sq.m days 1 and 8, etoposide 60 mg/sq.m days 1-3 and cisplatin 75 mg/sq.m day 1 each 28 days for 6 cycles. There were 31 men and 9 women, being the average age of 54 years, with "performance Status" grade 0-2. All of them could be evaluated for toxicity and 31 for responsiveness. 10 patients were in stage IIIb and 21 at stage IV. 42% of objective responses were obtained and an overall survival of 9 months, which justifies further studies.

Estudio en fase II de navelbine + cisplatino + etoposido en el tratamiento del cáncer de pulmón no células pequeñas inoperable. / [Phase II trial with navelbine + cisplatin + etoposide in the treatment of inoperable non-small cell lung carcinoma]

40 patients with advanced non-small cell lung cancer not previously treated were included in a study at phase II with vinorelbine 20 mg/Sq.m days 1 and 8, etoposide 60 mg/sq.m days 1-3 and cisplatin 75 mg/sq.m day 1 each 28 days for 6 cycles. There were 31 men and 9 women, being the average age of 54 years, with [quot ]performance Status[quot ] grade 0-2. All of them could be evaluated for toxicity and 31 for responsiveness. 10 patients were in stage IIIb and 21 at stage IV. 42

of objective responses were obtained and an overall survival of 9 months, which justifies further studies.