Phase II Study of a Non‐Platinum–Containing Doublet of Paclitaxel and Pemetrexed with Bevacizumab as Initial Therapy for Patients with Advanced Lung Adenocarcinomas. Issue 6 (June 2016)

• Record Type: Journal Article
• Authors: Pietanza, M. C.; Hellmann, Matthew D.; Fiore, John J.; Smith‐Marrone, Stephanie; Basch, Ethan M.; Schwartz, Lawrence H.; Ginsberg, Michelle S.; Shouery, Marwan; Newman, Samantha K.; Shaw, Mary; Rogak, Lauren J.; Lash, Alex E.; Hilden, Patrick; Kris, Mark G.
• Is Part Of: Journal of thoracic oncology. Volume 11:Issue 6(2016)
• Publication Date: 2016-06
• Subjects: Lung adenocarcinomas -- Bevacizumab -- Nonplatinum chemotherapy -- Pemetrexed -- Paclitaxel; Chest -- Cancer -- Periodicals; Thoracic Neoplasms -- Periodicals; 616.99494005
• DOI: 10.1016/j.jtho.2016.02.018
• Languages: English
• ISSNs: 1556-0864

Abstract

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.