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/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.