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The risk of brain metastasis after response to epidermal growth factor receptor tyrosine kinase inhibitor in non-small cell lung cancer
Yonsei Cancer Center; Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 1
*Young Joo Lee1, Byoung Chul Cho1, Hye Jin Choi1, Joo-Hang Kim1
Purpose: This study was designed to evaluate the incidence of brain metastasis as the first failure after an initial response to EGFR TKI in advanced non-small cell lung cancer (NSCLC). Methods: We reviewed 265 patients with stage IIIB/IV NSCLC treated with gefitinib or erlotinib at Severance hospital between 2002 and 2008.We focused on 103 patients who had a more than 3 month of time to progression (TTP). Results: Patient (n= 103) and disease characteristics included median age 58 years; female (n= 58, 56%); never smoker (n= 62, 60%);
adenocarcinoma and/or bronchoalveolar carcinoma (n= 76, 74%); and EGFR mutations (n= 44, 43%). During the median follow-up duration of 24.5 months, 74 patients (72%) experienced disease progression after an initial response. The initial sites of disease progression included lung (n= 43, 58%), brain (n= 15, 20%), and others (n= 16, 22%). Among 15 patients with brain metastasis, 10 patients (66.6%) had lung disease under control at the time of brain metastasis. The incidence of only brain metastasis as an initial failure was more increased in patients with EGFR mutations compared with in patients with wild type EGFR although the difference was not statistically significant (22.7% versus 10.7%, P = 0.06). When subjects were restricted to patients with TTP> 6 months (n= 43), the incidence of brain metastasis as an initial failure was increased to 28.3% (n= 8). In total patients with TTP> 3 months, the median overall survival time were 9.8 months and 18.2 months for patients with and without brain metastasis, respectively (P= 0.14). Conclusions: The incidence of brain metastasis is high in advanced NSCLC responding to EGFR TKI. This may lead to prophylactic cranial irradiation strategy or the more careful monitoring for early detection in asymptomatic responder to EGFR TKI.
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Lapatinib and capecitabine in HER2-Positive metastatic breast cancer
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea1 Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Korea2
*Yongjun Cha,1, Jiyoung Rhee1, Ki Hwan Kim1, Sae-Won Han1, Do-Youn Oh1, Jee-Hyun Kim2, Seock-Ah Im1, Yung-Jue Bang1, and Tae-You Kim1
Background: To evaluate the efficacy and safety of lapaptinib and capecitabine combination chemotherapy in metastatic breast cancer (MBC) patients, 43% of whom has history of capecitabine treatment. Methods: A total of 37 female patients with HER2-positive MBC that had progressed after treatments with trastuzumab, anthracycline, and taxane-based chemotherapy were enrolled in an open-label expanded-access study of lapatinib (GlaxoSmithKline, USA) plus capecitabine at Seoul National University Hospital from Mar 2007 to Apr 2008.Patients received lapatinib (1, 250mg/day, D1-21) and capecitabine (2, 000mg/m2, D1-14) every 3weeks. The clinical data were prospectively collected. Results: Median age was 52 years (31-70). Performance status was ECOG 0 in one and 1 in thirty-six patients. Median follow-up duration was 9.1 months. Best overall response was partial response (PR) in 9 (24%), stable disease (SD) in 22 (59%), and progressive disease in 6 (16%) patients. Median progression-free survival (PFS) was 5.6 months (95% CI 4.0-7.3). Overall survival has not been reached yet. There was no significant difference in response rate/ disease control rate (DCR: PR + SD) and PFS according to prior capecitabine exposure (Table 1). Prior capecitabine treatment had been discontinued due to disease progression during treatment in 13 patients. Among these patients with resistance to capecitabine, lapatinib and capecitabine resulted in DCR/PFS comparable to that of patients without prior exposure to capecitabine. The major grade 3/4 toxicities include: hand-foot syndrome (14%), diarrhea (5%), asthenia (3%), vomiting (3%) sinusitis (3%), hypokalemia (3%), hyperbilirubinemia (3%), and neutropenia (1%). Conclusion: Lapatinib in combination with capecitabine demonstrated similar clinical activity irrespective of prior capecitabine exposure.
Table 1.Outcomes according to prior capecitabine treatment
No. of patients RR (%) P-value DCR (%) P-value Median PFS (mo) P-value
Prior capecitabine Yes 16 19 .70 81 >.99 4.7 .36
No 21 29 86 6.2
