Patel Shetal A, Gerber David E, Deal Allison, Douglas Kathe, Pecot Chad V, Lee Carrie, Schiller Joan, Dhruva Nirav, Weiss Jared
Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States.
Front Oncol. 2021 Apr 12;11:666691. doi: 10.3389/fonc.2021.666691. eCollection 2021.
Induction with four cycles of platinum-based chemotherapy was the standard of care for metastatic non-small cell lung cancer (NSCLC) until the approval of immune checkpoint blockade (ICB) in the first-line setting. Switch maintenance therapy has shown promise in improving survival by exposing patients to novel, non-cross-resistant agents earlier in their treatment course.
We performed this open-label, three-arm, randomized phase II study (NCT02684461) to evaluate three sequences of consolidation with pembrolizumab and nab-paclitaxel in patients without progressive disease post induction chemotherapy. Consolidation was either sequential with pembrolizumab for four cycles followed by nab-paclitaxel for four cycles (P→A), nab-paclitaxel followed by pembrolizumab (A→P), or concurrent nab-paclitaxel and pembrolizumab for four cycles (AP).
Twenty patients were randomized before the study was closed early due to the approval of first-line checkpoint inhibitors. We found that consolidation is feasible and well tolerated, with 30% of patients experiencing grade 3 toxicity. The median progression-free survival and OS in months (95% CI) in P→A were 10.1 (1.5-NR), 27.6 (1.7-NR); 8.4 (1.2-9.0), 12.7 (4.4-NR) in A→P; and 10.2 (5.1-NR), NR. Quality of life as measured by FACT-L improved in the majority of patients during the course of the study.
Sequential and concurrent consolidation regimens are well tolerated and have encouraging overall survival in patients with metastatic NSCLC.
在一线治疗中免疫检查点阻断（ICB）获批之前，四个周期的铂类化疗诱导是转移性非小细胞肺癌（NSCLC）的标准治疗方案。转换维持治疗通过在患者治疗过程中更早地使用新型、无交叉耐药的药物，在改善生存方面显示出前景。
我们开展了这项开放标签、三臂、随机II期研究（NCT02684461），以评估在诱导化疗后无疾病进展的患者中，帕博利珠单抗和白蛋白结合型紫杉醇三种巩固治疗顺序。巩固治疗要么是先给予帕博利珠单抗四个周期，随后给予白蛋白结合型紫杉醇四个周期（P→A），要么是先给予白蛋白结合型紫杉醇，随后给予帕博利珠单抗（A→P），要么是白蛋白结合型紫杉醇与帕博利珠单抗同时给药四个周期（AP）。
由于一线检查点抑制剂获批，该研究提前结束，共有20例患者被随机分组。我们发现巩固治疗是可行的且耐受性良好，30%的患者出现3级毒性。P→A组的中位无进展生存期和总生存期（月，95%CI）分别为10.1（1.5-未达到）、27.6（1.7-未达到）；A→P组为8.4（1.2-9.0）、12.7（从4.4-未达到）；AP组为10.2（5.1-未达到）、未达到。在研究过程中，大多数患者通过FACT-L测量的生活质量得到改善。
序贯和同时进行的巩固治疗方案耐受性良好，对转移性NSCLC患者的总生存期有令人鼓舞的效果。
