Successful osimertinib rechallenge following subsequent chemotherapy regimen in a patient with metastatic non-small cell lung carcinoma: a case report.

Although tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have a favorable and durable treatment response, almost all patients will eventually acquire resistance and develop disease progression. Re-administration of first and second-generation EGFR TKIs has been successfully executed in advanced non-small cell lung cancer (NSCLC) subsequent to EGFR-TKI resistance. However, osimertinib rechallenge following osimertinib resistance in EGFR T790M-negative patient is less explored. Herein, we describe a metastatic adenocarcinoma NSCLC patient with exon 19 deletion in EGFR (19del) who acquired resistance to initial gefitinib and second-line osimertinib but was successfully rechallenged with osimertinib following treatment failure with chemotherapy. The osimertinib rechallenge, despite the absence of EGFR T790M, was considered after the development of multiple small pulmonary lesions and an increase in EGFR exon 19 deletion. After a month of osimertinib rechallenge, pulmonary and brain lesions significantly reduced achieving partial response. The success of osimertinib rechallenge following previous osimertinib resistance in a metastatic NSCLC patient with EGFR 19del in the absence of T790M suggests that re-administration of osimertinib can be a treatment option in similar situations. In addition, this case also highlights the importance of mutational profiling for treatment monitoring to understand the mutational landscape of the patient and guide subsequent treatment including treatment rechallenge.

Lazarus type response to immunotherapy in three patients with poor performance status and locally advanced NSCLC: a case series and literature review.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). However, the safety and efficacy of ICIs in severe advanced NSCLC patients with poor performance status (PS) are still unclear. METHODS: In the current study, we report a retrospective case series of three critically ill NSCLC patients with poor PS treated with immunotherapy in our hospital, and discussed these cases with reference to the existing literature and guidelines. RESULTS: Before treatment, the Eastern Cooperative Oncology Group (ECOG) PS scores of all three patients were 4, while programmed cell death protein ligand-1 (PD-L1) was strongly expressed (over 50%). After initiating anti-programmed cell death 1 (PD-1)/PD-L1 agents, the PS score of the three patients improved rapidly to 0-1 in a short time. A Lazarus type response was observed in all patients. There were no grade 3-4 immune-related adverse events (irAEs) in any of the patients, and only one patient developed rash (grade 2 irAE) and hypothyroidism (grade 2 irAE). The best response across all three patients was partial response (PR). As of the latest follow-up date on June 10, 2020, two patients are still alive, with the other having died on January 14, 2020, whose progression-free survival (PFS) and overall survival (OS) were 11 and 16 months, respectively. CONCLUSIONS: Immunotherapy is still an effective and low-toxicity option for severe advanced NSCLC patients with poor PS. Lazarus type response may occur, especially in patients whose PD-L1 is strongly expressed (≥50%). However, a greater amount of real-world data or randomized clinical trials are needed in this setting.

Bone metastasis from lung cancer identified by genetic profiling.

Cancer metastasis remains responsible for the vast majority of cases of cancer-related morbidity and mortality. Metastasis, by its definition, is the spread of cancer from the primary site to the distant tissues. Advancing the scientific and clinical understanding of cancer metastasis is a high priority. The prerequisite requirement for pathological consistency may be compromised during metastasis. The present study reports the case of a cancer patient with different pathological types. The patient presented with pain in the neck and right hip, as well as weight loss. He underwent whole-body positron emission tomography-computed tomography, which identified a mass in the lung and abnormal metabolism of the bone. Biopsies of the ilium and lung were performed and he was shown to have lung adenocarcinoma and bone squamous carcinoma. The morphology and immunohistochemical patterns were completely different, while each lesion harbored an identical genetic profile. The bone lesion was identified to be a metastasis from the lung cancer. The patient was prescribed an epithelial growth factor receptor inhibitor, which resulted in a partial response in the lung mass and alleviation of the patient's bone pain. Through this case study, we advocate the importance of using genetic testing in addition to pathological assessment.

Neutrophil-lymphocyte ratio as a prognostic marker for chemotherapy in advanced lung cancer.

BACKGROUND: Lung cancer ranks first both in morbidity and mortality in malignancies, but prognostic biological markers are lacking. The neutrophil-lymphocyte ratio (NLR) was proposed as a convenient biological marker. This study aimed to explore the prognostic value of NLR in advanced non-small cell lung cancer (NSCLC). METHODS: This retrospective study screened patients admitted from October 2007 to October 2014. Patients had histopathologically confirmed, treatment-naïve, metastatic NSCLC, and were prescribed platinum doublet chemotherapy. NLR and demographic data were collected, together with the outcome of chemotherapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression model. RESULTS: A total of 325 patients were enrolled. The cutoff value for NLR (3.19) was determined by receiver operator characteristic analysis. Patients were dichotomized into high (≥3.19) and low (<3.19) NLR groups. Both groups had similar demographic features. However, the low-NLR group had longer PFS (6.1 months) and OS (22.3 months) than the high-NLR group (5.1 months, p = 0.002; 13.1 months, p<0.001, respectively). Multivariate analysis confirmed that NLR was inversely related to the prognosis of these patients (HR = 1.684, 95%: 1.297-2.185, p<0.001). CONCLUSIONS: This study argues that NLR is a convenient prognostic biological marker for advanced NSCLC patients treated with first-line chemotherapy and warrants further validation.