M C Pietanza1, Matthew D Hellmann1, John J Fiore2, Stephanie Smith-Marrone2, Ethan M Basch3, Lawrence H Schwartz4, Michelle S Ginsberg5, Marwan Shouery6, Samantha K Newman7, Mary Shaw6, Lauren J Rogak6, Alex E Lash8, Patrick Hilden6, Mark G Kris9. 1. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. 2. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 3. University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina. 4. Department of Radiology, Columbia University Medical Center, New York Presbyterian Hospital, New York, New York. 5. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiology, Weill Cornell Medical College, New York, New York. 6. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. 7. Department of Medicine, NYU School of Medicine, New York, New York. 8. Simons Foundation, New York, New York. 9. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. Electronic address: krism@mskcc.org.
Abstract
INTRODUCTION: Many patients with lung cancers cannot receive platinum-containing regimens owing to comorbid medical conditions. We designed the PPB (paclitaxel, pemetrexed, and bevacizumab) regimen to maintain or improve outcomes while averting the unique toxicities of platinum-based chemotherapies. METHODS: We enrolled patients with untreated, advanced lung adenocarcinomas with measurable disease and no contraindications to bevacizumab. Participants received paclitaxel, 90 mg/m(2), pemetrexed, 500 mg/m(2), and bevacizumab, 10 mg/kg, every 14 days for 6 months and continued to receive pemetrexed and bevacizumab every 14 days until progression or unacceptable toxicity. RESULTS: Of the 44 patients treated, 50% were women; the median age was 61 years and 89% had a Karnofsky performance status of at least 80%. We genotyped 38 patients with the following results: Kirsten rat sarcoma viral oncogene homolog gene (KRAS), 16; anaplastic lymphoma receptor tyrosine kinase gene (ALK), three; B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E, two; erb-b2 receptor tyrosine kinase 2 gene (HER2)/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), one; epidermal growth factor receptor gene (EGFR) exon 20 insertion, one; and driver 15, none. A total of 23 patients achieved a PR (52%, 95% confidence interval: 37-68), including seven of 16 with KRAS-mutant tumors. The overall survival rate at 2 years was 43% with a median of 17 months (95% confidence interval: 10-29). Grade 3/4 treatment-related toxicities included elevated alanine transaminase level (16%), fatigue (16%), leukopenia (9%), anemia (7%), elevated aspartate transaminase level (7%), edema (5%), and pleural effusions (5%). Two patients died of respiratory failure without disease progression. CONCLUSIONS: The PPB regimen produced a high response rate in patients with lung adenocarcinomas regardless of mutational status. Survival and toxicities were comparable to those in the phase II reports testing platinum-containing doublets with bevacizumab. These results justify use of the PPB regimen in fit patients in whom three-drug regimens including bevacizumab are appropriate.
INTRODUCTION: Many patients with lung cancers cannot receive platinum-containing regimens owing to comorbid medical conditions. We designed the PPB (paclitaxel, pemetrexed, and bevacizumab) regimen to maintain or improve outcomes while averting the unique toxicities of platinum-based chemotherapies. METHODS: We enrolled patients with untreated, advanced lung adenocarcinomas with measurable disease and no contraindications to bevacizumab. Participants received paclitaxel, 90 mg/m(2), pemetrexed, 500 mg/m(2), and bevacizumab, 10 mg/kg, every 14 days for 6 months and continued to receive pemetrexed and bevacizumab every 14 days until progression or unacceptable toxicity. RESULTS: Of the 44 patients treated, 50% were women; the median age was 61 years and 89% had a Karnofsky performance status of at least 80%. We genotyped 38 patients with the following results: Kirsten ratsarcoma viral oncogene homolog gene (KRAS), 16; anaplastic lymphoma receptor tyrosine kinase gene (ALK), three; B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E, two; erb-b2 receptor tyrosine kinase 2 gene (HER2)/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), one; epidermal growth factor receptor gene (EGFR) exon 20 insertion, one; and driver 15, none. A total of 23 patients achieved a PR (52%, 95% confidence interval: 37-68), including seven of 16 with KRAS-mutant tumors. The overall survival rate at 2 years was 43% with a median of 17 months (95% confidence interval: 10-29). Grade 3/4 treatment-related toxicities included elevated alanine transaminase level (16%), fatigue (16%), leukopenia (9%), anemia (7%), elevated aspartate transaminase level (7%), edema (5%), and pleural effusions (5%). Two patients died of respiratory failure without disease progression. CONCLUSIONS: The PPB regimen produced a high response rate in patients with lung adenocarcinomas regardless of mutational status. Survival and toxicities were comparable to those in the phase II reports testing platinum-containing doublets with bevacizumab. These results justify use of the PPB regimen in fit patients in whom three-drug regimens including bevacizumab are appropriate.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Fabrice Barlesi; Arnaud Scherpereel; Achim Rittmeyer; Antonio Pazzola; Neus Ferrer Tur; Joo-Hang Kim; Myung-Ju Ahn; Joachim G J V Aerts; Vera Gorbunova; Anders Vikström; Elaine K Wong; Pablo Perez-Moreno; Lada Mitchell; Harry J M Groen Journal: J Clin Oncol Date: 2013-07-08 Impact factor: 44.544
Authors: Ethan Basch; David Artz; Alexia Iasonos; John Speakman; Kevin Shannon; Kai Lin; Charmaine Pun; Henry Yong; Paul Fearn; Allison Barz; Howard I Scher; Mary McCabe; Deborah Schrag Journal: J Am Med Inform Assoc Date: 2007-02-28 Impact factor: 4.497
Authors: Wallace Akerley; James E Herndon; Merrill J Egorin; Alan P Lyss; Hedy L Kindler; Dianne M Savarese; Carol A Sherman; D Marc Rosen; Donna Hollis; Mark J Ratain; Mark R Green Journal: Cancer Date: 2003-05-15 Impact factor: 6.860
Authors: Giorgio Vittorio Scagliotti; Purvish Parikh; Joachim von Pawel; Bonne Biesma; Johan Vansteenkiste; Christian Manegold; Piotr Serwatowski; Ulrich Gatzemeier; Raghunadharao Digumarti; Mauro Zukin; Jin S Lee; Anders Mellemgaard; Keunchil Park; Shehkar Patil; Janusz Rolski; Tuncay Goksel; Filippo de Marinis; Lorinda Simms; Katherine P Sugarman; David Gandara Journal: J Clin Oncol Date: 2008-05-27 Impact factor: 44.544
Authors: Ethan Basch; William A Wood; Deborah Schrag; Camelia S Sima; Mary Shaw; Lauren J Rogak; Mark G Kris; Marwan Shouery; Antonia Bennett; Thomas Atkinson; M Catherine Pietanza Journal: Clin Trials Date: 2015-11-04 Impact factor: 2.486
Authors: Egbert F Smit; Jan P A M van Meerbeeck; Pilar Lianes; Channa Debruyne; Catherine Legrand; Franz Schramel; Hans Smit; Rabab Gaafar; Bonne Biesma; Chris Manegold; Niels Neymark; Giuseppe Giaccone Journal: J Clin Oncol Date: 2003-11-01 Impact factor: 44.544
Authors: Barbara A Conley; Lou Staudt; Naoko Takebe; David A Wheeler; Linghua Wang; Maria F Cardenas; Viktoriya Korchina; Jean Claude Zenklusen; Lisa M McShane; James V Tricoli; Paul M Williams; Irina Lubensky; Geraldine O'Sullivan-Coyne; Elise Kohn; Richard F Little; Jeffrey White; Shakun Malik; Lyndsay N Harris; Bhupinder Mann; Carol Weil; Roy Tarnuzzer; Chris Karlovich; Brian Rodgers; Lalitha Shankar; Paula M Jacobs; Tracy Nolan; Sean M Berryman; Julie Gastier-Foster; Jay Bowen; Kristen Leraas; Hui Shen; Peter W Laird; Manel Esteller; Vincent Miller; Adrienne Johnson; Elijah F Edmondson; Thomas J Giordano; Benjamin Kim; S Percy Ivy Journal: J Natl Cancer Inst Date: 2021-01-04 Impact factor: 11.816