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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 in patients with LM depending on EGFR status. aEGFR wild-type NSCLC patients who received standard first-line chemotherapy presented a clear benefit in terms of OS when liver was not involved (n = 96) compared to those patients with LM (n = 45). b No differences were observed in EGFR mutated population receiving first line TKI in terms of OS when comparing patients with no LM (n = 13) with patients with liver involvement (n = 4).
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Fig3: OS in patients with LM depending on EGFR status. aEGFR wild-type NSCLC patients who received standard first-line chemotherapy presented a clear benefit in terms of OS when liver was not involved (n = 96) compared to those patients with LM (n = 45). b No differences were observed in EGFR mutated population receiving first line TKI in terms of OS when comparing patients with no LM (n = 13) with patients with liver involvement (n = 4).

Mentions: Subsequently, we analyzed the impact on the OS of the EGFR TKIs treatment in those patients with EFGR mutant tumors receiving first-line targeted therapy, according to the presence or absence of secondary liver involvement. On the one hand, when the OS analysis was restricted to EGFR wild-type NSCLC patients who received standard first-line chemotherapy, a clear benefit in OS was observed in favor of individuals without liver involvement compared to those patients with liver disease [23 months (95% CI 13.1–32.9) vs. 13 months (95% CI 8.1–17.9), respectively; p = 0.001]. In fact, those subjects showing liver involvement presented a 117% higher risk of death than patients with no liver involvement (HR = 2.17), (Fig. 3a). Interestingly enough and in contrast with our previous results, liver involvement lost its prognostic impact among patients with EGFR mutated tumors receiving first-line EGFR TKIs therapy. Thus, a non-statistically significant benefit in OS in subjects without liver metastases compared to those with liver involvement was observed [median OS not reached (95% CI N.R.) vs. 25 months (95% CI 15.8–34.1); p = 0.81], (Fig. 3b).Fig. 3


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 in patients with LM depending on EGFR status. aEGFR wild-type NSCLC patients who received standard first-line chemotherapy presented a clear benefit in terms of OS when liver was not involved (n = 96) compared to those patients with LM (n = 45). b No differences were observed in EGFR mutated population receiving first line TKI in terms of OS when comparing patients with no LM (n = 13) with patients with liver involvement (n = 4).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: OS in patients with LM depending on EGFR status. aEGFR wild-type NSCLC patients who received standard first-line chemotherapy presented a clear benefit in terms of OS when liver was not involved (n = 96) compared to those patients with LM (n = 45). b No differences were observed in EGFR mutated population receiving first line TKI in terms of OS when comparing patients with no LM (n = 13) with patients with liver involvement (n = 4).
Mentions: Subsequently, we analyzed the impact on the OS of the EGFR TKIs treatment in those patients with EFGR mutant tumors receiving first-line targeted therapy, according to the presence or absence of secondary liver involvement. On the one hand, when the OS analysis was restricted to EGFR wild-type NSCLC patients who received standard first-line chemotherapy, a clear benefit in OS was observed in favor of individuals without liver involvement compared to those patients with liver disease [23 months (95% CI 13.1–32.9) vs. 13 months (95% CI 8.1–17.9), respectively; p = 0.001]. In fact, those subjects showing liver involvement presented a 117% higher risk of death than patients with no liver involvement (HR = 2.17), (Fig. 3a). Interestingly enough and in contrast with our previous results, liver involvement lost its prognostic impact among patients with EGFR mutated tumors receiving first-line EGFR TKIs therapy. Thus, a non-statistically significant benefit in OS in subjects without liver metastases compared to those with liver involvement was observed [median OS not reached (95% CI N.R.) vs. 25 months (95% CI 15.8–34.1); p = 0.81], (Fig. 3b).Fig. 3

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