Citations 2
Adjuvant nab -Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial
Tempero, Margaret A. , Pelzer, Uwe , Oh, Do‐Youn , Li, Chung‐Pin , Tortora, Giampaolo , Chang, Heung-Moon, Lopez, Charles D. , Bekaii‐Saab, Tanios , Ko, Andrew H. , Santoro, Armando , Noel, Marcus Smith , Dean, Andrew , Riess, Hanno, Philip, Philip, Moore, Malcolm J. , Goldstein, David , Ferrara, Stefano, Bruchec, Yvan Le, Lu, Brian , Epstein, Richard A. , Vasey, Paul L., Shapiro, Jeremy, Burge, Matthew , Chua, Yu Jo , Harris, Marion , Prager, Gerald W. , Dittrich, Christian , Längle, Friedrich, Philipp‐Abbrederis, Kathrin, Greil, Richard , Stöger, Herbert, Girschikofsky, Michael , Kuehr, Thomas, Laethem, Jean–Luc Van, Laurent, Stéphanie , Ko, Yoo Joung, Dowden, Scot, Kavan, Petr , Tehfe, Mustapha Édouard, Kubala, Eugen, Kohoutek, Milan, Yilmaz, Mette, Parner, Vibeke K., Salminen, Tapio , Soveri, Leena‐Maija , Korkeila, Eija, Taı̈eb, Julien , Artru, Pascal , Guimbaud, Rosine , Turpin, Antony, Kunzmann, Volker , Kreth, Florian, Oettle, Helmut, Karthaus, Meinolf , Folprecht, Gunnar , Kullmann, Frank , Reiser, Marcel , Heinemann, Volker , Wörns, Marcus‐Alexander , Schulz, H. , Garlipp, Benjamin , Chan, Lam Stephen, Juhász, Balázs , Landherr, László, Pintér, Tamás , Kahán, Zsuzsanna , McDermott, Raymond, Power, Derek G. , Siena, Salvatore, Milella, Michèle , Bagalá, Cinzia, Roila, Fausto, Fanello, Silvia, Wilmink, Johanna W. , Groot, Jan Willem de, Creemers, G.J., Rodrigues, Tânia , Tai, David , Mercadé, T. Macarulla, Medina, Manuel Hidalgo, Mena, Alfredo Carrato, Santasusana, Joan Maurel, Oncala, Maria Jose Flor, Martín, Carlos Gómez , Muñoz, Andrés, García, Ruth Vera, Alés, Inmaculada, Rivera, Fernando , Sastre, Javier , Wu, Cheng‐Chung, Tien, Yu‐Wen , Chan, De-Chuan , Hwang, Tsann‐Long , Evans, Jeffry, Wadsley, Jonathan , Chiorean, E. Gabriela , Bendell, Johanna C. , Kindler, Hedy L. , Fernando, Nishan H., Beg, Muhammad Shaalan , LoConte, Noelle K. , Posey, James , Malhotra, Rajat, Sohal, Davendra , Brenner, Warren, Womack, Mark, Seth, Rahul , lyer, Renuka, Bahary, Nathan , Marsh, Robert , Chua, Cynthia C., Reeves, J. N. , Manji, Gulam A. , Sahai, Vaibhav , Messersmith, Wells A. , Zakari, Ahmed, Bullock, Andrea J. , Musher, Benjamin , Kim, Edward , Bajor, David J., Huyck, Tim, Hatoum, Hassan , Xiong, Henry, Pasche, Boris , Lacy, Jill , Olowokure, Olugbenga, Cohn, Allen Lee, Richards, Donald , Martin, Robert C.G. , Paulson, Andrew Scott , Fanta, Paul T. , Krishnamurthi, Smitha , Fuloria, Jyotsna, McDermott, Ray , Turpin, Anthony , O'Reilly, Eileen M , Winter, Jordan Michael , Oh, Do-Youn , Li, Chung-Pin , Tortora, Giampaolo , Bekaii-Saab, Tanios S , Santoro, Armando , Park, Joon Oh , Dean, Andrew , Van Cutsem, Eric , Berlin, Jordan D. , Tabernero, Josep , Biankin, Andrew V , LoConte, Noelle , Taieb, Julien , McDermott, Ray , Prager, Gerald W , Sahai, Vaibhav , O’Reilly, Eileen M. , Frassineti, Giovanni Luca , Shan, Yan‐Shen , Cutsem, Eric Van , Tabernero, Josep , Li, Mingyu , Zhang, George , Biankin, Andrew V. , Reni, Michele , Vasey, Paul, Pavlakis, Nick , Tebbutt, Niall C. , Längle, Friedrich, Dhani, Neesha C. , Tehfe, Mustapha , Pfeiffer, Per , Osterlund, Pia J. , Tougeron, David , Caroli‐Bosc, François‐Xavier , Walter, Thomas , Bachet, Jean‐Baptiste , Block, Andreas, Venerito, Marino , Trojan, Jörg , Lerch, Markus M. , Schulz, Holger, Yau, Thomas , Juhasz, Balazs, Bodoky, Gyorgy , Gianni, Luca , Siena, Salvatore , Falcone, Alfredo , Berardi, Rossana , Costanzo, Francesco Di , Ardizzoni, Andrea , Maiello, Evaristo , Barroso, Eduardo , Sarmento, Cristina, Chee, Cheng Ean , López López, Rafael , Sáez, Berta Laquente, Chan, De‐Chuan , Evans, Jeffry, Corrie, Pippa G. , Cardin, Dana B. , Noonan, Anne M. , George, Thomas J. , Arena, Francis P. , McWilliams, Robert R. , Seth, Rahul, Ramirez, Robert A. , Reeves, James, El-Khoueiry, Anthony B. , Weaver, Robert, Dreicer, Robert , Borad, Mitesh J. , Huyck, Timothy K., Xiong, Henry Q., Oberstein, Paul E.
Journal of Clinical Oncology | December 15, 2022 | Volume: 41 | Issue: 11 | Pages: 2007-2019
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 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m 2 ) + gemcitabine (1,000 mg/m 2 ) 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. RESULTS Two 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. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
Regorafenib for Patients with Metastatic Colorectal Cancer Who Progressed After Standard Therapy: Results of the Large, Single-Arm, Open-Label Phase IIIb CONSIGN Study
Cascinu, Stefano , Sobrero, Alberto F. , Banzi, Maria , Seitz, Jean‐François, Barone, Carlo , Brenner, Baruch , Hofheinz, Ralf‐Dieter , Spallanzani, Andrea , García‐Carbonero, Rocio , Arriaga, Yull , Verma, Udit, Kappeler, Christian, Miriyala, Ashok, Kalmus, J., Falcone, Alfredo , Zaniboni, Alberto , Falcone, Alfredo , Cutsem, Eric Van , Martinelli, Erika , Ychou, Marc , Peeters, Marc , Maiello, Evaristo , André, Thierry , Grothey, Axel
The Oncologist | September 6, 2018 | Volume: 24 | Issue: 2 | Pages: 185-192
10.1634/theoncologist.2018-0072
Abstract Background In the phase III CORRECT trial, regorafenib significantly improved survival in treatment-refractory metastatic colorectal cancer (mCRC). The CONSIGN study was designed to further characterize regorafenib safety and allow patients access to regorafenib before market authorization. Methods This prospective, single-arm study enrolled patients in 25 countries at 186 sites. Patients with treatment-refractory mCRC and an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1 received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle. The primary endpoint was safety. Progression-free survival (PFS) per investigator assessment was the only efficacy evaluation. Results In total, 2,872 patients were assigned to treatment and 2,864 were treated. Median age was 62 years, ECOG PS 0/1 was 47%/53%, and 74% had received at least three prior regimens for metastatic disease. Median treatment duration was three cycles. Treatment-emergent adverse events (TEAEs) led to dose reduction in 46% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 9%. Grade 5 regorafenib-related TEAEs occurred in <1%. The most common grade ≥3 regorafenib-related TEAEs were hypertension (15%), hand–foot skin reaction (14%), fatigue (13%), diarrhea (5%), and hypophosphatemia (5%). Treatment-emergent grade 3–4 laboratory toxicities included alanine aminotransferase (6%), aspartate aminotransferase (7%), and bilirubin (13%). Ongoing monitoring identified one nonfatal case of regorafenib-related severe drug-induced liver injury per DILI Working Group criteria. Median PFS (95% confidence interval [CI]) was 2.7 months (2.6–2.7). Conclusion In CONSIGN, the frequency and severity of TEAEs were consistent with the known safety profile of regorafenib. PFS was similar to reports of phase III trials. ClinicalTrials.gov: NCT01538680. Implications for Practice Patients with metastatic colorectal cancer (mCRC) who fail treatment with standard therapies, including chemotherapy and monoclonal antibodies targeting vascular endothelial growth factor or epidermal growth factor receptor, have few treatment options. The multikinase inhibitor regorafenib was shown to improve survival in patients with treatment-refractory mCRC in the phase III CORRECT (N = 760) and CONCUR (N = 204) trials. However, safety data on regorafenib for mCRC in a larger number of patients were not available. The CONSIGN trial, carried out prospectively in more than 2,800 patients across 25 countries, confirmed the safety profile of regorafenib from the phase III trials and reinforced the importance of using treatment modifications to manage adverse events.