Abstract
Introduction
Anaplastic lymphoma kinase (ALK) gene translocation occurs in 3%–5% of patients with non-small cell lung cancer (NSCLC), typically in younger patients. Crizotinib (tyrosine kinase inhibitor) has been considered as the standard of care for advanced ALK-positive lung cancer but it only gives a median progression-free survival of 7.7–11 months.
Case
A 41-year-old old man, former smoker, was diagnosed with NSCLC in the right lung with manifest pleural effusion. This case was complicated by a pleural empyema and because of a trapped lung, there was an indication for the construction of a thoracostomy. After confirmation of the ALK translocation, therapy with crizotinib was started. After 8 weeks, there was excellent response, and 6 months later, all lesions were undetectable on CT scan. There was also complete healing of the thoracostomy wound.
Conclusion
This case describes a relatively young patient with a poor prognosis but with a remarkable and long-term response to crizotinib monotherapy.
Introduction
Anaplastic lymphoma kinase (ALK) gene translocation occurs in 2%–7% of cases of non-small cell lung cancer (NSCLC), typically in younger patients.1,2 Crizotinib targets this mutation because it is an oral A adenosine triphosphate–competitive selective inhibitor of ALK. 2 Phase III trials have shown crizotinib to be superior to standard chemotherapy for the first- or second-line treatment of advanced ALK-positive lung cancer. 1 Since 2014, crizotinib has been considered as the standard of care for ALK-positive lung cancer. Its success is due to outstanding results and good tolerability and safety profile. 3 As many patients are diagnosed when the disease is already in an incurable stage, treatment with crizotinib generally results in a median progression-free survival of only 9.7–11.1 months.4–6 More specifically, in the locally advanced or metastatic setting, treatment with crizotinib showed a median progression-free survival of 7.7 months. 7 Alectinib is gaining importance because of superior efficacy and lower toxicity. 5 We report an excellent long-term result of crizotinib.
Case report
The patient consulted a pneumologist in April 2014. He was a 41-year-old former smoker without significant medical history. His symptoms began in January 2014 with dyspnea, especially when lying on his right side. There was suspicion of a pleuropneumonia (Figure 1), but analysis on pleural fluid confirmed the diagnosis of non-small cell lung adenocarcinoma (NSCLC). The cancer was limited to the right lung and the right pleural cavity. Further investigations (computed tomography [CT] of the thorax and abdomen and magnetic resonance imaging of the brain) did not show extrathoracic metastases. The disease was classified as stage cT4 N0 M1a because of multiple lung nodules and malignant pleural fluid. While awaiting the results of the ALK mutation analysis, the patient sought several second opinions. At that time, no experimental therapy was available, so standard treatment with cisplatin plus pemetrexed was started, which was tolerated moderately well by the patient. After 2 cycles, he experienced aggravation of dyspnea, related to increase of the pleural fluid; therefore an attempt was made to carry out thoracoscopic decortication and pleurodesis. This attempt failed because of a trapped lung. Subsequently the patient developed a pleural empyema with Escherichia coli in July 2014, which was treated with ciprofloxacin/clindamycin and simultaneous thorax drainage. Admission to intensive care was necessary and the patient and his family were informed of the likely very poor prognosis. Classical treatment with thoracic drains and antibiotics did not result in any improvement. Video-assisted thoracoscopy empyema washout was an option but because of the trapped lung, which had no possibility of expanding, a dead space was formed that could not be sterilized. The patient was very septic, so this situation was considered an indication for the construction of a thoracostomy. During this procedure, the pleural cavity was filled with 3 boxes of sterile vaginal wick. It was feared that the malignant pleurisy would grow into this wound and the tumor would prevent healing of the wound. Around this time, the mutation analysis was completed: an ALK translocation was confirmed and there was no epidermal growth factor receptor mutation. Because of aggravation of symptoms, second-line therapy with crizotinib was initiated according to the guidelines of that period. After 8 weeks from the start, there was a nearly complete response visible on CT scan and 6 months later all lesions were undetectable (Figure 2). Follow-up was provided every 12 weeks, with a CT scan performed each time. During the treatment, a steady healing of the thoracostomy wound was seen, with less use of wick to sterilize it until it was completely healed.
X-ray of the thorax at time of diagnosis.
Evolution on computed tomography scans.
Discussion
This case is remarkable because of several characteristics. First, it describes a relatively young patient with a poor prognosis but with an excellent response to crizotinib therapy. There is one similar case published in the literature in 2016, where the authors describe a patient with NSCLC with brain metastases who showed stable disease during 24 months under crizotinib. 8 In 2015, a case report was published about a patient treated with crizotinib for 8 months who showed complete pathologic remission during the therapy period, whereafter the therapy was ended as wished by the patient. 9 In 1 phase 3 trial and 2 phase 1 trials, a total of 6 complete remissions were described but the total duration of the response is unknown.2,4,5 In one of the trials, Camidge et al. 4 report a median progression-free survival of almost 10 months. The patient showed full remission of all the lesions, and most importantly, the response lasted at least 4 years until now. During this time, the patient had an excellent quality of life with no hospitalization and minimal side effects of the therapy, just some flashes of light and peripheral edema. Another interesting finding is the spontaneous healing of the thoracostomy wound, which is for this indication a very rare event.
Conclusion
We present a young patient with a diagnosis of a late stage of NSCLC complicated by a pleural empyema requiring a thoracostomy. A short survival time was expected but this patient responded well to the crizotinib therapy, with full remission of 4 years. No equally long-lasting response was found in the literature, where median progression-free survival is described between 7.7 and 11 months. This case proves that excellent results can occur with crizotinib therapy in patients with advanced ALK-positive NSCLC.
Footnotes
Declaration of conflicting interest
The authors received no financial support for the research, authorship, or publication of this article.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
