EGFR–TKIs linked to reduced chemotherapy sensitivity in NSCLC

By Laura Cowen, medwireNews Reporter

Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs) appear to significantly reduce the efficacy of subsequent chemotherapy in patients with EGFR-mutated non-small-cell lung cancer (NSCLC), Chinese researchers report.

EGFR–TKIs are given as a standard first-line treatment to patients with EGFR-mutated NSCLC, but when they fail, chemotherapy may be used as a second-line strategy.

However, there is “clinical concern” that “frontline EGFR TKI treatment may influence subsequent chemo-sensitivity in clinical practice”, explain Yi-long Wu and colleagues from Guangdong General Hospital in Guangzhou.

To investigate whether this is the case, Wu and team reviewed data for 203 patients with EGFR-mutated NSCLC who underwent treatment at the Guangdong Lung Cancer Institute between 2006 and 2012.

The cohort included 68 patients who received first-line EGFR–TKI followed by chemotherapy and 135 who received first-line chemotherapy followed by an EGFR–TKI. The majority (92.1%) of chemotherapy regimens given were platinum-based and gefitinib was slightly more commonly used than erlotinib (n=113 vs 90 patients).

The researchers report in Lung Cancer that the response rate (RR) to chemotherapy was significantly higher for patients who received it as a first-line treatment compared with those who received it after EGFR-TKI therapy, at 34.1% versus 13.2%.

EFGR–TKI naïve patients also had significantly longer progression-free survival (PFS) and overall survival times than the EFGR–TKI refractory patients, at 6.9 and 31.7 months versus 3.9 and 23.5 months, respectively.

Furthermore, multivariate analysis confirmed that first-line EGFR–TKI treatment was an independent risk factor for a lack of response to chemotherapy, disease progression and mortality, at respective hazard ratios of 3.39, 3.06 and 1.91.

However, the researchers caution that the difference in overall survival between the two groups may be partly due to selection bias as patients who did not experience disease progression while receiving an EGFR–TKI would not have received post-TKI treatment and therefore not have been enrolled in this study.

Of note, the RR and PFS during EGFR–TKI therapy were similar regardless of whether it was used as a first- (76.5% and 11.0 months) or second-line (68.9% and 10.2 months) treatment, indicating that although “TKI treatment may lead to a significantly reduced efficacy of subsequent chemotherapy”, the reverse is not true, Wu et al remark.

They conclude: “For EGFR mutant patients, the influence of EGFR-TKI on subsequent chemotherapy will be critical in establishing the sequence and timing of EGFR-TKI vs conventional chemotherapy in the management of advanced NSCLC, we are looking forward to more data from randomized trial[s] to validate our findings.”

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