PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430).METHODSWe assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety.RESULTSTwo hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 (nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P =.18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P =.02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P =.045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 (nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P =.0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P =.0091). Eighty-six percent (nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events.CONCLUSIONThe primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
Tempero, M. A., Pelzer, U., O'Reilly, E. M., Winter, J., Oh, D. -., Li, C. -., Tortora, G., Chang, H. -., Lopez, C. D., Bekaii-Saab, T., Ko, A. H., Santoro, A., Park, J. O., Noel, M. S., Frassineti, G. L., Shan, Y. -., Dean, A., Riess, H., Van Cutsem, E., Berlin, J., Philip, P., Moore, M., Goldstein, D., Tabernero, J., Li, M., Ferrara, S., Le Bruchec, Y., Zhang, G., Lu, B., Biankin, A. V., Reni, M., Epstein, R., Vasey, P., Shapiro, J., Burge, M., Chua, Y. J., Harris, M., Pavlakis, N., Tebbutt, N., Prager, G., Dittrich, C., Langle, F., Philipp-Abbrederis, K., Greil, R., Stoger, H., Girschikofsky, M., Kuehr, T., Van Laethem, J. -., Laurent, S., Dhani, N., Ko, Y. J., Dowden, S., Kavan, P., Tehfe, M. E., Kubala, E., Kohoutek, M., Pfeiffer, P., Yilmaz, M., Parner, V., Salminen, T., Soveri, L. -., Korkeila, E., Osterlund, P., Taieb, J., Tougeron, D., Artru, P., Caroli-Bosc, F. X., Guimbaud, R., Turpin, A., Walter, T., Bachet, J. B., Kunzmann, V., Kreth, F., Block, A., Venerito, M., Oettle, H., Karthaus, M., Trojan, J., Folprecht, G., Lerch, M., Kullmann, F., Reiser, M., Heinemann, V., Worns, M. -., Schulz, H., Garlipp, B., Yau, T., Chan, L. S., Juhasz, B., Landherr, L., Pinter, T., Bodoky, G., Kahan, Z., Mcdermott, R., Power, D., Gianni, L., Siena, S., Milella, M., Falcone, A., Berardi, R., Bagala, C., Di Costanzo, F., Roila, F., Ardizzoni, A., Maiello, E., Fanello, S., Wilmink, J., Willem De Groot, J., Creemers, G., Barroso, E., Rodrigues, T., Sarmento, C., Chee, C. E., Tai, D., Mercade, T. M., Medina, M. H., Mena, A. C., Santasusana, J. M., Flor Oncala, M. J., Martin, C. G., Lopez, R., Munoz, A., Garcia, R. V., Ales, I., Saez, B. L., Rivera, F., Sastre, J., Wu, C. -., Tien, Y. -., Chan, D. -., Hwang, T. -., Evans, J., Wadsley, J., Corrie, P., Biankin, A., Ko, A., Cardin, D., Chiorean, E., Bendell, J., Noonan, A., Kindler, H., Fernando, N., Beg, M., George, T., Noel, M., Loconte, N., Arena, F., Posey, J., Malhotra, R., Lopez, C., Sohal, D., Mcwilliams, R., Brenner, W., Womack, M., Seth, R., Lyer, R., Bahary, N., Marsh, R., Ramirez, R., Chua, C., Reeves, J., Manji, G., El-Khoueiry, A., Weaver, R., Sahai, V., Messersmith, W., Dreicer, R., Zakari, A., Bullock, A., Musher, B., Borad, M., Kim, E., Bajor, D., Huyck, T., Hatoum, H., Xiong, H., Pasche, B., Lacy, J., Olowokure, O., Cohn, A., Richards, D., Martin, R., Paulson, A., Fanta, P., Krishnamurthi, S., Oberstein, P., Fuloria, J., Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results from a Randomized, Open-Label, Phase III Trial, <<JOURNAL OF CLINICAL ONCOLOGY>>, 2023; 41 (11): 2007-2019. [doi:10.1200/JCO.22.01134] [https://hdl.handle.net/10807/304684]
Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results from a Randomized, Open-Label, Phase III Trial
Tortora, Giampaolo;Gianni, Leonardo;Maiello, Emanuela;
2023
Abstract
PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430).METHODSWe assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety.RESULTSTwo hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 (nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P =.18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P =.02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P =.045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 (nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P =.0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P =.0091). Eighty-six percent (nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events.CONCLUSIONThe primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
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