Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Thorac Cancer. 2020 Oct;11(10):2916-2923. doi: 10.1111/1759-7714.13631. Epub 2020 Aug 24.
The PACIFIC study has defined a new standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) in the form of immune checkpoint inhibitor (ICI) consolidation therapy. However, there is little specific data pertaining to the safety and efficacy of this approach in Chinese NSCLC patients.
This was a prospective multicenter cohort study. Between September 2018 and January 2020, patients with unresectable stage III NSCLC that had undergone chemoradiation therapy (CRT) and ICI consolidation treatment were enrolled in this study. The short-term safety, tolerability, and efficacy of ICI combination with CRT were evaluated in these patients.
Of the 20 Chinese patients eligible for inclusion, 17 (85.0%) underwent concurrent CRT treatment. In these patients, a median period of 40.5 days (range: 1-85 days) passed between the end of CRT and initiation of consolidation therapy. Pneumonitis occurred in 80.0% of patients, with seven (35.0%) being diagnosed with grade 1 pneumonitis and nine (45.0%) with grade 2 pneumonitis. No patients experienced grade 3 or higher pneumonitis or other ICI-related toxicities. Lung V20 ≥ 20% was associated with higher grade 2 pneumonitis (77.8%; ≥20% vs. 18.2%; <20%, P = 0.027). The overall response rate (ORR) in these patients was 95.0%. Over a median follow-up period of 11.3 months (range: 6.2-21.8 months), 12-month PFS of these patients were 89.5% (95% CI: 76.7-100.0%), and 12 months OS was 100.0%.
These data indicate that ICI consolidation therapy can achieve favorable short-term efficacy, while exhibiting good safety and acceptable toxicity profiles in Chinese patients with unresectable stage III NSCLC.
Significant findings of the study This is the first report evaluating the safety and efficacy of ICI consolidation therapy after chemoradiotherapy in China. Our results indicate that ICI consolidation is associated with favorable efficacy and no severe pneumonitis incidence in Chinese patients undergoing both anti-PD-1 and anti-PD-L1 monoclonal antibody consolidation. What this study adds Post-hoc analysis of the Japanese subgroup in the PACIFIC study suggested that consolidation therapy may be associated with increased pneumonitis incidence in Asian patients. However, our findings indicate that consolidation therapy is safe and tolerable in Chinese patients with unresectable stage III NSCLC.
PACIFIC 研究为不可切除 III 期非小细胞肺癌（NSCLC）患者的免疫检查点抑制剂（ICI）巩固治疗确立了新的治疗标准。然而，关于这种方法在中国 NSCLC 患者中的安全性和疗效的具体数据很少。
这是一项前瞻性多中心队列研究。2018 年 9 月至 2020 年 1 月，招募了接受不可切除的 III 期 NSCLC 患者，这些患者已接受放化疗（CRT）和 ICI 巩固治疗。评估了这些患者接受 CRT 联合 ICI 的短期安全性、耐受性和疗效。
在符合纳入条件的 20 例中国患者中，17 例（85.0%）接受了同步 CRT 治疗。在这些患者中，CRT 结束与巩固治疗开始之间中位时间为 40.5 天（范围：1-85 天）。80.0%的患者发生肺炎，7 例（35.0%）为 1 级肺炎，9 例（45.0%）为 2 级肺炎。无患者发生 3 级或更高级别的肺炎或其他 ICI 相关毒性。肺 V20≥20%与较高的 2 级肺炎相关（77.8%；≥20% vs. 18.2%；<20%，P=0.027）。这些患者的总缓解率（ORR）为 95.0%。在中位随访 11.3 个月（范围：6.2-21.8 个月）期间，这些患者的 12 个月 PFS 为 89.5%（95%CI：76.7-100.0%），12 个月 OS 为 100.0%。
这些数据表明，ICI 巩固治疗在中国不可切除 III 期 NSCLC 患者中可获得良好的短期疗效，且安全性良好，毒性可接受。
研究的重要发现 这是第一项评估中国接受放化疗后接受 ICI 巩固治疗的安全性和疗效的研究。我们的结果表明，ICI 巩固治疗与接受抗 PD-1 和抗 PD-L1 单克隆抗体巩固治疗的中国患者发生的有利疗效和无严重肺炎发生率相关。 本研究的新增内容 对 PACIFIC 研究的日本亚组的事后分析表明，巩固治疗可能与亚洲患者的肺炎发生率增加相关。然而，我们的研究结果表明，ICI 巩固治疗在中国不可切除 III 期 NSCLC 患者中是安全且耐受的。
