PTPRF Expression as a Potential Prognostic/Predictive Marker for Treatment with Erlotinib in Non-Small-Cell Lung Cancer

Introduction:EGFR mutations and anaplastic lymphoma kinase rearrangements are, to date, the only approved biomarkers to select treatment for non-small-cell lung cancer (NSCLC). However, there is considerable interest in identifying other predictive markers. The PTPRF gene has been suggested as a marker of interest in NSCLC and other tumor types. Methods: This hypothesis-generating retrospective analysis examined data from two studies of erlotinib in NSCLC, Marker Identification Trial (MERIT; n = 102) and Sequential Tarceva in Unresectable NSCLC (SATURN; n = 262), to determine whether PTPRF expression was prognostic and/or predictive of patient outcomes. Exploratory analyses were conducted using quantitative reverse transcription polymerase chain reaction on existing formalin-fixed paraffin-embedded samples, to assess gene expression levels, including PTPRF. High versus low levels of expression were dichotomized using the median with B2M as a control comparator. Progression-free survival and overall survival were then compared for patients with high versus low levels of PTPRF in the two studies. Results:PTPRF expression was found to be prognostic for shorter overall survival but was also significantly predictive of improved survival with erlotinib versus placebo in SATURN (hazard ratio, 0.45 [95% confidence interval, CI, 0.30-0.69] in PTPRF high versus 0.96 [95% CI, 0.62-1.48] in PTPRF low; interaction p = 0.02), even in the EGFR wild-type subpopulation (adjusted hazard ratio, 0.44 [95% CI, 0.29-0.68] versus 0.96 [95% CI, 0.62-1.48]; interaction p = 0.01). Conclusions:PTPRF may have value as a predictive marker to identify which patients can obtain the greatest benefit from erlotinib in the post-first-line setting. Further research is warranted to determine the potential value of this marker in clinical decision-making.