Complete remission of ALK-positive lung cancer in a patient after multiple lines of targeted therapy – a case study

Medical History and Diagnosis

A 55-year-old man presented to the local hospital in January 2018 due to a recurring dry cough over the past year, which was now accompanied by fever.

PET-CT examination of the lungs revealed an extensive lesion in the right hilum with obstructive pneumonia and a soft mass in the lower left lobe. Several lesions were also detected in the lymph nodes (e.g., near the left hilum and in the right adrenal gland). Histopathological examination of the biopsy revealed pulmonary adenocarcinoma, and molecular testing showed ALK and PD-L1 positivity with ROS1 and EGFR negativity. The patient was diagnosed with stage IV ALK-positive pulmonary adenocarcinoma with metastasis to the right adrenal gland.

Treatment Course

Targeted Therapy

Crizotinib treatment was initiated, and the patient achieved a partial response within the first month, with a reduction in the primary tumor and metastatic lesion. By the third month of treatment, the metastatic lesion had completely disappeared, but the primary tumor progressed after five months. Ceritinib treatment was then started, achieving a partial response, but progression occurred after six months. Alectinib was given as the third-line treatment, but the disease continued to progress.

Chemotherapy

The patient was then treated with chemotherapy combined with anti-angiogenic therapy (four cycles of pemetrexed/carboplatin/bevacizumab followed by maintenance therapy with pemetrexed/bevacizumab), achieving a partial response before disease progression after six months. One cycle of cetuximab with liposomal paclitaxel and nedaplatin was then administered, but no therapeutic response was observed.

Immunotherapy Combined with an ALK Inhibitor

In the sixth line of treatment, the patient received nine cycles of camrelizumab (an immune checkpoint inhibitor) with lorlatinib. A PET-CT performed in August 2020 showed increased uptake of the radioactive marker in the tumor mass in the left lung lobe, with a defect in the central tumor mass and no presence of metastases. Surgery was recommended.

Surgical Intervention

In September 2020, a thoracoscopically assisted left pneumonectomy, lymph node resection, and pleural adhesion ligation were performed. Postoperative pathological examination revealed massive necrosis of nodules in both the lower and upper left lung lobes, with no evident tumor tissue, focal granulomatous inflammation, clear resection margins, and no metastases in the lymph nodes. Complete remission of the primary lesion was achieved as assessed by the pathologist.

Conclusion

From October 2020 until the case was published (November 2022), the patient continued maintenance therapy with lorlatinib without adverse effects and remains in performance status 1 as per ECOG. No new lesions have been detected, and clinical remission of systemic disease has been achieved. This case thus demonstrates the potential benefit of immunotherapy after multiple lines of treatment for ALK-positive NSCLC.

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Source: Que D., Zou H., Mao B. et al. Pathological complete remission in ALK-positive lung cancer patient after multiple lines of conversion therapy. Front Oncol 2022 Nov 29; 12: 967675, doi: 10.3389/fonc.2022.967675.