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22-04-2014 | Article

Type of first-line therapy used in NSCLC could affect subsequent therapy options


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medwireNews: Being healthy enough to receive subsequent therapy after first-line treatment has failed in patients with non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations could be affected by the order in which targeted and standard therapies are given, report researchers.

Only one (3%) patient in their study who was treated with standard cytotoxic chemotherapy was unable to receive subsequent EGFR tyrosine kinase inhibitor (TKI) monotherapy, compared with nine (39%) of those who received a EGFR-TKI first.

The main reason why NSCLC patients who received first-line EGFR-TKI therapy failed to cross over to cytotoxic chemotherapy was due to symptomatic central nervous system (CNS) relapse, note the study authors in Cancer Chemotherapy and Pharmacology.

They explain that the movement of anticancer agents into cerebrospinal fluid is usually prevented by the blood–brain barrier. “However, the blood–brain barrier has already been destroyed by the time tumors are radiologically evident, and most cytotoxic chemotherapeutic agents can then infiltrate the CNS”, they add.

Despite the findings, the researchers, led by Katsuyuki Hotta (Okayama University, Japan), observed no survival differences between patients who received first-line EGFR-TKI and those who received cytotoxic chemotherapy.

A total of 23 patients in the study received first-line EGFR-TKI therapy, more often with gefitinib, while 40 received standard cytotoxic chemotherapy, a doublet of platinum and a new cytotoxic agent. All patients subsequently developed progressive disease.

Symptomatic CNS metastasis occurred more frequently in the EGFR-TKI therapy group, at 26% versus 10% in the cytotoxic chemotherapy group, as did worsening of performance status (an Eastern Cooperative Oncology Group score ≥ 3), at 21.7% versus 5.0%.

Hotta and colleagues suggest that both factors are likely to have contributed to the high percentage (39%) of patients in the first-line EGFR-TKI group who failed to receive subsequent cytotoxic chemotherapy.

Multivariate analysis confirmed a significant association between first-line therapy type and the failure to receive both treatment regimens, with EGFR-TKI as first-line therapy increasing this risk 48.6-fold.

“For the next step, it would be essential to detect pretreatment clinical or molecular characteristics of those unlikely to benefit from both therapies for development of a new treatment strategy”, suggest the researchers who hope that such a strategy would lead to survival improvement in NSCLC patients with EGFR mutations.

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014

By Sarah Pritchard, medwireNews Reporter