Stefano Cascinu1, Rossana Berardi2, Roberto Bianco3, Domenico Bilancia4, Alberto Zaniboni5, Daris Ferrari6, Stefania Mosconi7, Andrea Spallanzani8, Luigi Cavanna9, Silvana Leo10, Francesca Negri11, Giordano D Beretta12, Alberto Sobrero13, Maria Banzi14, Alberto Morabito15, Alessandro Bittoni2, Roberta Marciano3, Domenica Ferrara4, Silvia Noventa5, Maria C Piccirillo16, Roberto Labianca7, Cristina Mosconi17, Andrea Casadei Gardini18, Ciro Gallo19, Francesco Perrone16. 1. Medical Oncology Department, Università Vita-Salute, IRCCS-Ospedale San Raffaele, Milano, Italy. Electronic address: cascinu.stefano@hsr.it. 2. Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliera Umberto I, Salesi, Lancisi, Ancona, Italy. 3. Università Federico II Napoli, Italy. 4. Medical Oncology Unit, Ospedale San Carlo, Potenza, Italy. 5. Medical Oncology Unit, Fondazione Poliambulanza, Brescia, Italy. 6. Medical Oncology Unit, Azienda Ospedaliera San Paolo, Milano, Italy. 7. Cancer Center ASST Papa Giovanni XXIII, Bergamo, Italy. 8. Medical Oncology Unit, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy. 9. Medical Oncology Unit, Ospedale di Piacenza, Italy. 10. Medical Oncology Unit, Ospedale di Lecce, Italy. 11. Medical Oncology Unit, Azienda Ospedaliero-Universitaria di Parma, Italy. 12. Medical Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy. 13. Medical Oncology Unit, IRCCS San Martino-IST, Genova, Italy. 14. Medical Oncology Unit, Ospedale-IRCCS di Reggio Emilia, Italy. 15. Medical Oncology Unit Ospedale di Camposampiero, Italy. 16. Fondazione Istituto Nazionale Tumori-IRCCS G. Pascale, Napoli, Italy. 17. Istituto di Radiologia, Policlinico S. Orsola, Università di Bologna, Italy. 18. Medical Oncology Department, Università Vita-Salute, IRCCS-Ospedale San Raffaele, Milano, Italy. 19. Statistica Medica Università degli Studi della Campania Luigi Vanvitelli, Italy.
Abstract
BACKGROUND: The role of combination chemotherapy has not yet been established in unresectable locally advanced pancreatic cancer (LAPC) lacking dedicated randomized trials. METHODS: This phase II trial tested the efficacy of Nab-paclitaxel (NAB-P)/Gemcitabine (G) versus G alone. Patients were randomized, 1:1 to G 1000 mg/m2 on days 1, 8 and 15 every 28 days versus NAB-P 125 mg/m2 on days 1, 8 and 15 every 28 days plus G 1000 mg/m2 on days 1, 8 and 15 every 28 days. Disease progression rate after three cycles of chemotherapy was the primary end-point. Progression-free survival (PFS), overall survival (OS) and response rate were secondary end-points. FINDINGS:A total of124 patients were enrolled. The study showed a reduction of a progressive disease from 45.6% with G to 25.4% with NAB-P/G (P = 0.01) at 3 months. Noteworthy, at 6 months in the G arm, 35.6% of patients present a metastatic spread versus 20.8% in the NAB/G arm. The response rate was 5.3% in the G arm and 27% in the NAB/G arm. Median PFS was 4 months for the G arm and 7 months for the NAB-P/G arm. Median OS was 10.6 in the G arm and 12.7 months in the NAB-P/G arm. One patient died during treatment with G due to a stroke. INTERPRETATION: NAB-P/G reduced the rate of LAPC patients progressing after three cycles of chemotherapy compared with G, especially in terms of distant relapses. It positively affects PFS. To the best of our knowledge, this is the first randomized trial providing evidence that combination chemotherapy is superior to gemcitabine alone in this setting. CLINICALTRIALS. GOV IDENTIFIER: NCT02043730.
RCT Entities:
BACKGROUND: The role of combination chemotherapy has not yet been established in unresectable locally advanced pancreatic cancer (LAPC) lacking dedicated randomized trials. METHODS: This phase II trial tested the efficacy of Nab-paclitaxel (NAB-P)/Gemcitabine (G) versus G alone. Patients were randomized, 1:1 to G 1000 mg/m2 on days 1, 8 and 15 every 28 days versus NAB-P 125 mg/m2 on days 1, 8 and 15 every 28 days plus G 1000 mg/m2 on days 1, 8 and 15 every 28 days. Disease progression rate after three cycles of chemotherapy was the primary end-point. Progression-free survival (PFS), overall survival (OS) and response rate were secondary end-points. FINDINGS: A total of124 patients were enrolled. The study showed a reduction of a progressive disease from 45.6% with G to 25.4% with NAB-P/G (P = 0.01) at 3 months. Noteworthy, at 6 months in the G arm, 35.6% of patients present a metastatic spread versus 20.8% in the NAB/G arm. The response rate was 5.3% in the G arm and 27% in the NAB/G arm. Median PFS was 4 months for the G arm and 7 months for the NAB-P/G arm. Median OS was 10.6 in the G arm and 12.7 months in the NAB-P/G arm. One patient died during treatment with G due to a stroke. INTERPRETATION:NAB-P/G reduced the rate of LAPCpatients progressing after three cycles of chemotherapy compared with G, especially in terms of distant relapses. It positively affects PFS. To the best of our knowledge, this is the first randomized trial providing evidence that combination chemotherapy is superior to gemcitabine alone in this setting. CLINICALTRIALS. GOV IDENTIFIER: NCT02043730.
Authors: Zhan Shi; Ju Yang; Weiwei Kong; Xin Qiu; Changchang Lu; Juan Liu; Baorui Liu; Juan Du Journal: Front Oncol Date: 2022-03-01 Impact factor: 6.244