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Impact of epidermal growth factor receptor (EGFR) activating mutations and their targeted treatment in the prognosis of stage IV non-small cell lung cancer (NSCLC) patients harboring liver metastasis.

Castañón E, Rolfo C, Viñal D, López I, Fusco JP, Santisteban M, Martin P, Zubiri L, Echeveste JI, Gil-Bazo I - J Transl Med (2015)

Bottom Line: A total of 236 consecutive stage IV NSCLC patients treated at the Clínica Universidad de Navarra were analyzed.At onset, liver metastases were present in 16.9% of patients conferring them a shorter overall survival (OS) compared to those with different metastatic locations excluding liver infiltration (10 vs. 21 months; p = 0.001).Patients with EGFR wild-type tumors receiving standard chemotherapy and showing no liver involvement presented a superior median OS compared to those with liver metastases (23 vs. 13 months; p = 0.001).

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. ecastanon@unav.es.

ABSTRACT

Objectives: Liver metastases appear in 20-30% of patients diagnosed with non-small cell lung cancer (NSCLC) and represent a poor prognosis feature of NSCLC and a possibly more treatment-resistant condition. Potential clinical outcome differences in NSCLC patients with liver metastases harboring molecular alterations in EGFR, KRAS and EML4-ALK genes are still to be determined. This study aims to evaluate the incidence of liver metastasis in a single population and look for potential correlations between EGFR mutations, liver infiltration and clinical outcomes.

Methods: A total of 236 consecutive stage IV NSCLC patients treated at the Clínica Universidad de Navarra were analyzed.

Results: At onset, liver metastases were present in 16.9% of patients conferring them a shorter overall survival (OS) compared to those with different metastatic locations excluding liver infiltration (10 vs. 21 months; p = 0.001). Patients with EGFR wild-type tumors receiving standard chemotherapy and showing no liver involvement presented a superior median OS compared to those with liver metastases (23 vs. 13 months; p = 0.001). Conversely, patients with EGFR-mutated tumors treated with EGFR tyrosin-kinase inhibitors (TKI's) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 months; p = 0.81).

Conclusion: Overall, liver metastases at onset negatively impact OS of NSCLC patients. EGFR TKIs however, may reverse the effects of an initial negative prognosis of liver metastasis in first-line treatment of EGFR mutated NSCLC patients.

No MeSH data available.


Related in: MedlinePlus

OS depending on the EGFR status stratified by the presence of LM. a A subanalysis was performed selecting those patients with liver involvement. We observed a significant difference between those patients harboring EGFR mutations (n = 9) compared to those showing wild-type EGFR (n = 46). b When selecting patients with no liver involvement, we also observed a better outcome for those harboring EGFR mutation (n = 21) compared to those with EGFR wild type NSCLC (n = 98).
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Fig2: OS depending on the EGFR status stratified by the presence of LM. a A subanalysis was performed selecting those patients with liver involvement. We observed a significant difference between those patients harboring EGFR mutations (n = 9) compared to those showing wild-type EGFR (n = 46). b When selecting patients with no liver involvement, we also observed a better outcome for those harboring EGFR mutation (n = 21) compared to those with EGFR wild type NSCLC (n = 98).

Mentions: Additionally, a subanalysis was performed in order to study the impact of EGFR mutation status and the treatment with EGFR TKIs on the OS according to the presence or absence of liver involvement. Among patients with liver involvement, those with EGFR mutated tumors experienced a significantly superior OS compared to subjects with EGFR wild-type neoplasms [median OS not reached (95% CI not reached (N.R.)] vs. 13 months (95% CI 10.2–15.7), respectively; (HR = 0.06; p = 0.001) (Fig. 2a). Similarly, patients without liver involvement and EGFR mutated tumors showed a superior OS compared to those with EGFR wild type NSCLC [39 months (95% CI 20.2–57.8) vs. 23 months (95% CI 17.2–28.8); p = 0.047], (Fig. 2b).Fig. 2


Impact of epidermal growth factor receptor (EGFR) activating mutations and their targeted treatment in the prognosis of stage IV non-small cell lung cancer (NSCLC) patients harboring liver metastasis.

Castañón E, Rolfo C, Viñal D, López I, Fusco JP, Santisteban M, Martin P, Zubiri L, Echeveste JI, Gil-Bazo I - J Transl Med (2015)

OS depending on the EGFR status stratified by the presence of LM. a A subanalysis was performed selecting those patients with liver involvement. We observed a significant difference between those patients harboring EGFR mutations (n = 9) compared to those showing wild-type EGFR (n = 46). b When selecting patients with no liver involvement, we also observed a better outcome for those harboring EGFR mutation (n = 21) compared to those with EGFR wild type NSCLC (n = 98).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4528698&req=5

Fig2: OS depending on the EGFR status stratified by the presence of LM. a A subanalysis was performed selecting those patients with liver involvement. We observed a significant difference between those patients harboring EGFR mutations (n = 9) compared to those showing wild-type EGFR (n = 46). b When selecting patients with no liver involvement, we also observed a better outcome for those harboring EGFR mutation (n = 21) compared to those with EGFR wild type NSCLC (n = 98).
Mentions: Additionally, a subanalysis was performed in order to study the impact of EGFR mutation status and the treatment with EGFR TKIs on the OS according to the presence or absence of liver involvement. Among patients with liver involvement, those with EGFR mutated tumors experienced a significantly superior OS compared to subjects with EGFR wild-type neoplasms [median OS not reached (95% CI not reached (N.R.)] vs. 13 months (95% CI 10.2–15.7), respectively; (HR = 0.06; p = 0.001) (Fig. 2a). Similarly, patients without liver involvement and EGFR mutated tumors showed a superior OS compared to those with EGFR wild type NSCLC [39 months (95% CI 20.2–57.8) vs. 23 months (95% CI 17.2–28.8); p = 0.047], (Fig. 2b).Fig. 2

Bottom Line: A total of 236 consecutive stage IV NSCLC patients treated at the Clínica Universidad de Navarra were analyzed.At onset, liver metastases were present in 16.9% of patients conferring them a shorter overall survival (OS) compared to those with different metastatic locations excluding liver infiltration (10 vs. 21 months; p = 0.001).Patients with EGFR wild-type tumors receiving standard chemotherapy and showing no liver involvement presented a superior median OS compared to those with liver metastases (23 vs. 13 months; p = 0.001).

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. ecastanon@unav.es.

ABSTRACT

Objectives: Liver metastases appear in 20-30% of patients diagnosed with non-small cell lung cancer (NSCLC) and represent a poor prognosis feature of NSCLC and a possibly more treatment-resistant condition. Potential clinical outcome differences in NSCLC patients with liver metastases harboring molecular alterations in EGFR, KRAS and EML4-ALK genes are still to be determined. This study aims to evaluate the incidence of liver metastasis in a single population and look for potential correlations between EGFR mutations, liver infiltration and clinical outcomes.

Methods: A total of 236 consecutive stage IV NSCLC patients treated at the Clínica Universidad de Navarra were analyzed.

Results: At onset, liver metastases were present in 16.9% of patients conferring them a shorter overall survival (OS) compared to those with different metastatic locations excluding liver infiltration (10 vs. 21 months; p = 0.001). Patients with EGFR wild-type tumors receiving standard chemotherapy and showing no liver involvement presented a superior median OS compared to those with liver metastases (23 vs. 13 months; p = 0.001). Conversely, patients with EGFR-mutated tumors treated with EGFR tyrosin-kinase inhibitors (TKI's) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 months; p = 0.81).

Conclusion: Overall, liver metastases at onset negatively impact OS of NSCLC patients. EGFR TKIs however, may reverse the effects of an initial negative prognosis of liver metastasis in first-line treatment of EGFR mutated NSCLC patients.

No MeSH data available.


Related in: MedlinePlus