Que Dan, Zou Hongbo, Mao Bijing, Zhang Huan, Liang Wei, Liu Qin, Ke Leiyu, Guo Lijie, Xie Qichao
Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Medical Department, Shanghai OrigiMed Co., Ltd, Shanghai, China.
Front Oncol. 2022 Nov 29;12:967675. doi: 10.3389/fonc.2022.967675. eCollection 2022.
Traditional therapeutic approaches for the treatment of advanced non-small-cell lung cancer (NSCLC) are based on chemotherapy. However, the discovery and understanding of oncogenic driver alterations has led to the development of targeted therapies that have substantially improved patient outcomes. Still, to date, there have been no reports of patients with advanced anaplastic lymphoma kinase (ALK)-positive lung cancer achieving clinical complete response (cCR) in the systemic lesion and pathological complete remission (pCR) in primary lung lesion after multiple lines of conversion therapy.
In this case, a 55-year-old man was diagnosed with ALK-positive, stage IV lung adenocarcinoma using immunohistochemistry and next generation sequencing (NGS) tests.
Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, were used respectively as first-line, second-line, and third-line therapy. The patient received treatment with crizotinib and achieved partial response (PR), but 5 months later the efficacy was evaluated as progressive disease (PD). Ceritinib was used as the second-line treatment, but the disease progressed 6 months later. Alectinib was used as the third-line treatment, but the efficacy was evaluated as PD. From April 2019 to November 2019, the patient received 4 cycles of induction chemotherapy with pemetrexed/carboplatin/bevacizumab and then switched to pemetrexed/bevacizumab as the fourth-line treatment, and received the fifth line treatment, cetuximab/paclitaxel liposome/nedaplatin, for 1 cycle, but the disease still progressed. Then the patient received the sixth line of treatment, camrelizumab/lorlatinib, for 9 antitumor cycles, resulting in PR. The patient underwent surgery followed by maintenance treatment with lorlatinib and achieved cCR. To our knowledge, this is the first documented case of cCR in a patient with ALK-positive advanced lung adenocarcinoma treated with multiple lines of therapy followed by surgical treatment.
This case reveals the possible survival benefit of immunotherapy after multiple line treatment in ALK-positive advanced lung adenocarcinoma, indicating that it is possible find new therapeutic targets based on NGS molecular detection and provide precise therapeutic strategies for clinical practice when drug resistance or progression occurs in cancer therapy.
晚期非小细胞肺癌（NSCLC）的传统治疗方法以化疗为基础。然而，致癌驱动改变的发现和认识促使了靶向治疗的发展，显著改善了患者的治疗效果。尽管如此，迄今为止，尚无关于晚期间变性淋巴瘤激酶（ALK）阳性肺癌患者在经过多线转化治疗后全身病灶达到临床完全缓解（cCR）且原发性肺部病灶达到病理完全缓解（pCR）的报道。
在此病例中，一名55岁男性通过免疫组织化学和下一代测序（NGS）检测被诊断为ALK阳性IV期肺腺癌。
克唑替尼以及另外两种ATP竞争性ALK抑制剂色瑞替尼和阿来替尼分别被用作一线、二线和三线治疗。患者接受克唑替尼治疗并获得部分缓解（PR），但5个月后疗效评估为疾病进展（PD）。色瑞替尼用作二线治疗，但6个月后疾病进展。阿来替尼用作三线治疗，但疗效评估为PD。从2019年4月至2019年11月，患者接受了4个周期的培美曲塞/卡铂/贝伐单抗诱导化疗，然后转为培美曲塞/贝伐单抗作为四线治疗，并接受了一线西妥昔单抗/紫杉醇脂质体/奈达铂的第五线治疗，但疾病仍进展。随后患者接受了第六线治疗，即卡瑞利珠单抗/洛拉替尼，进行了9个抗肿瘤周期的治疗，获得了PR。患者接受了手术，随后用洛拉替尼进行维持治疗并实现了cCR。据我们所知，这是首例经多线治疗后接受手术治疗的ALK阳性晚期肺腺癌患者实现cCR的记录病例。
该病例揭示了ALK阳性晚期肺腺癌多线治疗后免疫治疗可能带来的生存益处，表明基于NGS分子检测有可能找到新的治疗靶点，并在癌症治疗出现耐药或进展时为临床实践提供精确的治疗策略。
