Phase II study of a non-platinum-containing doublet of paclitaxel and pemetrexed with bevacizumab as initial therapy for patients with advanced lung adenocarcinomas Journal Article

   

Authors:	Pietanza, M. C.; Hellmann, M. D.; Fiore, J. J.; Smith-Marrone, S.; Basch, E. M.; Schwartz, L. H.; Ginsberg, M. S.; Shouery, M.; Newman, S. K.; Shaw, M.; Rogak, L. J.; Lash, A. E.; Hilden, P.; Kris, M. G.
Article Title:	Phase II study of a non-platinum-containing doublet of paclitaxel and pemetrexed with bevacizumab as initial therapy for patients with advanced lung adenocarcinomas
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/m2, pemetrexed, 500 mg/m2, 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 sevenof 16withKRAS-mutant tumors. The overall survival rate at 2 years was 43% with a median of 17 months (95% confi-dence 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. © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Keywords:	bevacizumab; paclitaxel; pemetrexed; lung adenocarcinomas; nonplatinum chemotherapy
Journal Title:	Journal of Thoracic Oncology
Volume:	11
Issue:	6
ISSN:	1556-0864
Publisher:	Elsevier Inc.
Date Published:	2016-06-01
Start Page:	890
End Page:	899
Language:	English
DOI:	10.1016/j.jtho.2016.02.018
PROVIDER:	scopus
PMCID:	PMC4877255
PUBMED:	26964771
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979790736&partnerID=40&md5=1ca61cb9b550435b7ab5bae9d1a2bb1f
Notes:	Article -- Export Date: 1 September 2016 -- Source: Scopus

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