PTPRF Expression as a Potential Prognostic/Predictive Marker for Treatment with Erlotinib in Non-Small-Cell Lung Cancer.
BACKGROUND
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.
Department of Hematology, Centre Hospitalier de l'Université de Montréal, Montréal, Canada.
Denis
D
Soulières
Department of Medicine, University of Colorado Cancer Center, Aurora, Colorado.
Fred R
FR
Hirsch
Department of Medicine, University Health Network, princess Margaret Cancer Centre, Toronto, Canada.
Frances A
FA
Shepherd
Department of Clinical Science, Basel, Switzerland.
Walter
W
Bordogna
Statistics, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Paul
P
Delmar
Department of Oncology Biomarkers, Genentech Inc., SanFrancisco, California.
David S
DS
Shames
Department of Oncology Biomarkers, Genentech Inc., SanFrancisco, California. Electronic address: barbara.klughammer@roche.com.
Barbara
B
Klughammer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics* / Q000378:metabolism*
D000970:Antineoplastic Agents; D000069347:Erlotinib Hydrochloride; C516772:PTPRF protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2