Citations 2
Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study
Babiker, Hani M. , Picozzi, Vincent J. , Chandana, Sreenivasa R , Melichar, Bohuslav, Kasi, Anup , Gang, Jin, Gállego, Javier , Bullock, Andrea J. , Chunyi, Hao, Hitre, Erika, Osipov, Arsen , Alés, Inmaculada, Dragovich, Tomislav, Lee, Woo Jin , Feeney, Kynan, Ueno, Makoto , Seufferlein, Thomas , Investigators, on behalf of the PANOVA-3 Study, Osipov, Arsen, Matrana, Marc , Blondin, Nicholas, Shroff, Rachna T. , Orr, Douglas, Anderson, Michael J. , Shields, Anthony F. , Hamm, John , Bullock, Andrea, Nagireddy, Sumana, Kolodney, Joanna, Dragovich, Tomislav, Maniam, Ajit, Sears, Judith D., Stilwill, Joseph, Cusnir, Mike , Niewiaroska, Anna, Small, William, Kasi, Anup, Tache, Jason, Ross, Sharona, Shihabi, Samer, Gandhi, Sunil, Reeves, J. N. , Green, Garrett , Feinstein, Trevor, Huyck, Timothy K., Ramdin, Nadia, Marsh, Robert , Jiang, Yixing , Hatoum, Hassan , Manda, Sudhir, Kochenderfer, Mark D., Illum, Henrik, Richards, Donald , Valilis, P., Wong, Lucas, Newton, Herbert B. , Abdelrahim, Maen, Einspahr, David, Siegel, Richard, McKenney, Scott, Narang, Mohit , Cárdenes, Higinia R. , Thanikachalam, Kannan , Raff, Joshua P. , Ye, Joseph , Behl, Deepti , Kam, Audrey E., DeRose, Paul, Tasneem, A. , Brenner, Warren, Santos, Jennifer De Los , Rausch, D C, Trikha, Gaurav, Gabrail, Nashat , Mowat, Rex B., Jahangir, Khawaja, Schumaker, Robert P. , Soffen, Edward , Bravin, Eric, Gupta, Mukul Kumar , Bedoya-Apraez, Ivan Dario, Kang, Tyler Y., Lemay, Frédéric , Vincent, Mark , Létourneau, Richard, Doehring, Christine, Haberkorn, Mike, Rußwurm, Karen, Chater, Jack, Küng, Marc , Schacher, Sabine, Passhak, Maria , Geva, Ravit , Hubert, Ayala, Golan, Talia , Senellart, Hélène, Trouilloud, Isabelle , Blan, Jean-Frederic, Dourthe, Luis-Marie, Roy, Florence Le, Martin-Babau, J., Greil, Richard , Schreil, Georg, Gerger, Armin , Eisterer, Wolfgang , Mercadé, T. Macarulla, Cubillo, Antonio , Pons, Francesc Valladares, Díaz, Inmaculada Alés, Rivera, Fernando , Sarvise, Mariano Ponz, Airoldi, Mario , Bellotti, Giovanna, Corsi, Domenico , Antonuzzo, Lorenzo , Melichar, Bohuslav, Holečková, Petra , Kotasek, Rostislav, Němeček, Radim , Cutsem, Eric van, Laethem, Jean‐Luc Van , Sym, Sun Jin , Kim, Jin Young , Oh, Sang Cheul , Park, Joon Oh, Kim, Jin Won , Lee, Myung Ah , Choi, Hye Jin, Kang, Seok Yun , Mruk, Andrzej, Freier, Beata, Kosakowska, Ewa Anna, Kocsis, Judit, Csőszi, Tibor , Hitre, Erika, Al-Farhat, Yousuf, Cang, Shundong , Jin, Gang , Zuo, Changzeng, Song, Lijie, Wu, Zheng , Gao, Jie , Zhang, Tao� , Wang, Yusheng , Yuan, Xin , Li, Zhi-Hua , Chen, Rufu , Cai, Xiujun , Zhu, Zhizhen, Bai, Yuxian , Bai, Chunmei, Yau, Thomas, Joubert, Warren , Wong, Ka Yeung Mark, Harris, Marion , Mišir, Ana, Faccio, Adilson , Cruz, Felipe Melo , Azevedo, Srergio De, Victorino, Ana Paula , Paiva, Tadeu Ferreira, Franke, Fábio , Tiscoski, Katsuki Arima , Parolla, Gabriel, Lilno, Flora, Siqueira, Mariana Bruno , Lyra, Marcos, Lira, Jose Luis Martinez, Oliva, Dolores Mendoza, Vazquez, Arturo, Luviano, Jesus Elvis Cabrera, Gutiérrez, Erika Castillo , Camargo, Vanessa Rosas, Guerra, Cristian Chavez, Flores, Osvaldo Hernandez, Contreras, Jessica Reyes, Villanueva, Ángel Gómez, Villanueva, Omar Zayas, Bullock, Andrea , Wyrwicz, Lucjan , Osipov, Arsen , De La Fouchardiere, Christelle , Lee, Woojin , Ueno, Makoto , Van Cutsem, Eric , Macarulla, Teresa , Babiker, Hani , Antonuzzo, Lorenzo , Melichar, Bohuslav, Kasi, Anup , Gang, Jin, Gallego, Javier , Hitre, Erika, Fouchardière, Christelle de la , Dragovich, Tomislav, Philip, Philip A. , Cutsem, Eric Van , Macarulla, Teresa , Investigators, on behalf of the PANOVA-3 Study, Spigel, David R. , Osipov, Arsen, Lou, Emil , Bullock, Andrea, Dragovich, Tomislav, Coveler, Andrew L. , Arena, Francis P. , Kasi, Anup, Ross, Sharona , Reeves, James, Green, Garrett, Uemura, Marc Isamu , Ye, Joseph, Wang, James Z. , Rausch, Daniel, Park, Jae‐Hyun , Schumaker, Robert, Gupta, Mukul, Letourneau, Richard, Fuchs, Martin , Vogel, Arndt , Chater, Jack, Schacher, Sabine, Stemmer, Salomon M. , Dourthe, Luis-Marie, Abdelghani, Méher Ben , Pons, Francesc Valladares, Guillén‐Ponce, Carmen , Yayá, Ricardo , Ponz‐Sarvisé, Mariano , Vincenzi, Bruno , Melichar, Bohuslav, Petruzelka, Lubos B. , Cutsem, Eric van, Borbath, Ivan , Hwang, Jun‐Eul , Oh, Sung Yong , Lee, Moon Hee , Choi, Hye Jin , Chon, Hong Jae , Ramlau, Rodryg , Mruk, Andrzej, Hitre, Erika, Bassam, Ali, Hao, Chunyi , Liang, Bo , Li, Wei , Bai, Chunmei , Joubert, Warren, Marx, Gavin M. , Azevedo, Srergio De, Hoff, Paulo M. , Vazquez, Arturo, Guerra, Cristian Chavez, Cortez, David Orta, Campos-Gómez, Saúl , Espinoza, Iván Romarico González
Journal of Clinical Oncology | May 31, 2025 | Volume: 43 | Issue: 21 | Pages: 2350-2360
PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.
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.