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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Retrospective study of EGFR-mutant lung adenocarcinoma with bone metastatic clinical features
Liyan Gu1, Ting Gong1, Qing Ma1
1Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin, PR China.
Background:
With more and more target medicine application in lung cancer, lots of patients take medicine at home, the treatment bone metastasis and screen of bone metastasis always has been neglected until skeletal-related events (SREs) such as bone pain, hypercalcemia of malignancy and pathologic fractures emerging which significantly impairs the patients' daily activity ability, seriously lower quality of life.
Aim:
To identify the clinical characteristics of patients which influence the overall survival (OS) of EGFR-TKIs effective in EGFR-mutant NSCLC with bone metastasis (BM) and the bone metastatic image features.
Methods:
We conducted a retrospective study in patients (treated with EGFR-TKIs ≥6 months) of lung adenocarcinoma with BM in our hospital from October 2014 to October 2017. The Kaplan-Meier survival curves were calculated using the log-rank univariate test. Multivariate regression analysis was conducted using Cox's regression model. Comparison between the different subgroups of bone metastasis was conducted using Pearson Chi-Square test.
Results:
A total of 79 patients were diagnosed as EGFR-mutant lung adenocarcinoma with bone metastases. At univariate analysis, age < 65 years (p = .024), heavy smoking (p = .005), Osteolytic BM (p = .034), number of bone metastasis ≥3 (p = .032), EGFR-L858R mutated (p = .018) and bisphosphonate times <6 (p = .046), were significantly associated with worse overall survival (OS). At multivariate analysis, EGFR 19del was an independent predictor of better OS (p = .035). Osteolytic BM was more likely to occur in EGFR-mutant patients (osteolytic vs. sclerotic vs. mixed: 45.57% vs. 34.18% vs. 20.25%). Patients who had received bisphosphonate ≥6 times were less suffer from SRE compared to those treated with bisphosphonate <6 times (p = .019).
Conclusion:
In conclusions, this retrospective study suggests that for the patients, treated with EGFR-TKIs ≥6 months, EGFR exon 19 del, osteogenic bone metastasis, bisphosphonate application times ≥6, smoking <400/day and the number of BM <3 were predictors of better OS (p < .05). Bisphosphonate times ≥9 should be considered to the patients with BM. SPECT-CT would be an effective correction of SPECT in the patient's bone metastasis examination. During the whole follow-up process, we found by chance that the change of bone mineral density in the follow-up process suggested that bisphosphonates need to be used for more than 1 year or more, and we can use local CT in the follow-up clinical practice to confirm the bone density changes to decide when we could stop or reduce bisphosphonate application.
Insights
EGFR exon 19 deletion and osteogenic bone metastasis predict better survival in lung cancer patients on EGFR-TKIs. More bisphosphonate treatments improve outcomes, suggesting longer use for bone metastasis management.
Area of Science:
- Oncology
- Radiology
- Pharmacology
Background:
- Targeted therapies for lung cancer often involve home-based treatment, leading to neglect in monitoring and managing bone metastasis.
- Skeletal-related events (SREs) like bone pain and fractures significantly impair quality of life in lung cancer patients with bone metastasis.
- Early identification and management of bone metastasis are crucial for improving patient outcomes and daily functioning.
Purpose of the Study:
- To identify clinical characteristics influencing overall survival (OS) in EGFR-TKI-treated non-small cell lung cancer (NSCLC) patients with bone metastasis (BM).
- To analyze bone metastatic image features associated with survival outcomes.
- To evaluate the impact of bisphosphonate treatment duration on SREs and survival.
Main Methods:
- Retrospective study of 79 EGFR-mutant lung adenocarcinoma patients with BM treated with EGFR-TKIs for ≥6 months.
- Kaplan-Meier survival analysis and log-rank tests for univariate analysis.
- Cox regression model for multivariate analysis and Pearson Chi-Square test for subgroup comparisons.
Main Results:
- Univariate analysis identified age <65, heavy smoking, osteolytic BM, ≥3 bone metastases, EGFR-L858R mutation, and <6 bisphosphonate treatments as predictors of worse OS.
- Multivariate analysis revealed EGFR 19del as an independent predictor of better OS (p = 0.035).
- Osteolytic BM was more prevalent in EGFR-mutant patients. Bisphosphonate treatment ≥6 times correlated with fewer SREs.
Conclusions:
- EGFR exon 19 deletion, osteogenic bone metastasis, ≥6 bisphosphonate treatments, less smoking, and <3 bone metastases predict better OS in EGFR-TKI treated patients.
- Consider bisphosphonate treatment for ≥9 cycles in patients with bone metastasis.
- SPECT-CT can aid bone metastasis examination; monitoring bone density changes can guide bisphosphonate use duration.
