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
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.
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
J Thorac Oncol. 2016 Jun;11(6):890-9. doi: 10.1016/j.jtho.2016.02.018. Epub 2016 Mar 8.
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.
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.
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.
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.
许多肺癌患者由于合并其他疾病而无法接受含铂方案治疗。我们设计了PPB（紫杉醇、培美曲塞和贝伐单抗）方案，以维持或改善治疗效果，同时避免铂类化疗特有的毒性。
我们纳入了未经治疗的、具有可测量病灶且无贝伐单抗使用禁忌证的晚期肺腺癌患者。参与者每14天接受一次紫杉醇90mg/m²、培美曲塞500mg/m²和贝伐单抗10mg/kg的治疗，持续6个月，之后继续每14天接受培美曲塞和贝伐单抗治疗，直至病情进展或出现不可接受的毒性反应。
在接受治疗的44例患者中，50%为女性；中位年龄为61岁，89%的患者卡氏评分至少为80分。我们对38例患者进行了基因分型，结果如下： Kirsten大鼠肉瘤病毒癌基因同源物基因（KRAS）突变16例；间变性淋巴瘤激酶基因（ALK）突变3例；B-Raf原癌基因丝氨酸/苏氨酸激酶基因（BRAF）V600E突变2例；erb-b2受体酪氨酸激酶2基因（HER2）/磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α基因（PIK3CA）突变1例；表皮生长因子受体基因（EGFR）外显子20插入突变型1例；驱动基因未发现突变15例。共有23例患者达到部分缓解（PR，52%，95%置信区间：37%-68%），其中16例KRAS突变型肿瘤患者中有7例达到PR。2年总生存率为43%，中位生存期为17个月（95%置信区间：10-29个月）。3/4级治疗相关毒性包括丙氨酸转氨酶水平升高（16%）、疲劳（16%）、白细胞减少（9%）、贫血（7%）、天冬氨酸转氨酶水平升高（7%）、水肿（5%）和胸腔积液（5%）。2例患者死于呼吸衰竭，无疾病进展。
PPB方案在肺腺癌患者中产生了较高的缓解率，无论其突变状态如何。生存率和毒性与含铂双药联合贝伐单抗的II期报告中的结果相当。这些结果证明了PPB方案在适合使用包括贝伐单抗在内的三药方案的患者中的应用价值。
