1178PD - Common and rare EGFR mutations (EGFRm) in the RADIANT trial

Date 27 September 2014
Event ESMO 2014
Session NSCLC early stage, SCLC and other thoracic malignancies
Topics Non-Small Cell Lung Cancer
Pathology/Molecular Biology
Basic Scientific Principles
Presenter Wilfried Eberhardt
Citation Annals of Oncology (2014) 25 (suppl_4): iv409-iv416. 10.1093/annonc/mdu347
Authors W.E.E. Eberhardt1, F.A. Shepherd2, N.K. Altorki3, M.E.R. O'Brien4, J. Wang5, J. Wu6, S.C. Gill5, K.K. Iwata6, F.C. Richardson7, J.D. Horan8, M.A. Foley5, K. Kelly9
  • 1Department Of Medical Oncology, West German Cancer Centre, University Hospital Essen, 45122 - Essen/DE
  • 2University Health Network, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 3Thoracic Surgery, New Presbyterian Hospital -Weill Cornell Medical college, 10065 - New York City/US
  • 4Medical Oncology, Royal Marsden Hospital, SW36JJ - London/GB
  • 5Astellas Pharma Global Development, Astellas, 60062 - Northbrook/US
  • 6Astellas Scientific And Medical Affairs, Astellas, 60062 - Northbrook/US
  • 7Fc Richardson Consulting Ltc, FC Richardson Consulting LTC, 80027 - Louisville/US
  • 8Novella Clinical, Novella Clinical, 80305 - Boulder/US
  • 9Comprehensive Cancer Center, UC Davis, 95817 - Sacramento/US

Abstract

Aim

Data on EGFRm in early stage NSCLC are limited. RADIANT was a large prospectively randomized Ph3 trial of adjuvant erlotinib (E) v placebo (P) in patients (pts) with completely resected Stage IB to IIIA NSCLC that was EGFR positive by IHC or FISH (ASCO 14 #7501).

Methods

EGFRm in exons 18-21 were determined by WAVE® HS and confirmed by Sanger sequencing. Two EGFRm groups were defined: Common refers to pts with a del19 or L858R irrespective of the presence of another EGFRm; Rare Only refers to pts with a EGFRm without a del19 or L858R. Disease-free survival (DFS) analyses were performed by subgroup. Descriptive data are presented by mutation type for the Rare Only group.

Results

Of 921 pts with EGFRm status determined, 198 pts (21.5%) had EGFRm; 161 (17.5%) pts were in the Common group. In this group, 12 pts had another EGFRm in addition to del19 or L858R, including 2 pts with exon 20 mutations (1 with L858R+ T790M). The Rare Only group had 37 pts (4.0%). See data in tables below. Additional analyses of clinical characteristics will be presented.

EGFRm (n) Subgroup EGFRm Arm n DFS
Events Median (m) HR (E/P) 95% Cl
Common^ (161) Del 19/L858R E P 120 59 39 32 46.4 28.5 0.61 (0.38, 0.98)
Del 19 E P 56 33 23 17 46.4 26.4 0.68 (0.36, 1.28)
L858R E P 46 26 16 15 NR 29.3 0.55 (0.27, 1.12)
Rare Only (37) All E P 19 18 7 8 NR NR 1.30 (0.47, 3.60)
Exon 20 (21) E P 11 10 4 5 NR 35.0 1.09 (0.29, 4.09)
Rare Only (n)* Detail Arm n DFS Min, Max
Exon 18 G719X (8) G719A,G719A + E709A, G719A + E709K G719A E P 5 3 0.0 + , 45.6+ 33.2 + , 47.6+
Other Exon 18 (4) L692, G719A + E709A, G719A + E709K V689L E P 3 1 0.0 + , 28.2 48.1+
Exon 19 (2) R748T L747S E P 1 1 54.4+ 45.7+
Exon 20 Ins_dup (17) A767_S768Ins, H773_V774ins, V774_C775ins, A767_V769dup, N771_H773dup, A767_V769dup, P772_H773dup N771_H773dup, P772_H773ins, A767_V769dup, A763_Y764ins, H773dup E P 10 7 0.0 + , 40.0+ 16.2, 48.1+
Exon 20 other (4) S768I R776H, S768I + V774M, R776H E P 1 3 45.6+ 33.2 + , 45.6+
Exon 21 (8) L861Q, E868K D830N, L861Q, L844P, V845E E P 2 6 1.9, 42.1+ 1.8, 40.8+

NR = Not Reached. ^Includes 12 pts with another EGFRm in addition to del19 or L858R. + Indicates censoring; *Pts may have >1 rare EGFRm.

Conclusions

Rare Only EGFRm occurred in 18.7% (37/198) of pts with EGFRm in this population. The effect of E on DFS in EGFRm subgroups is inconclusive and needs further elucidation.

Disclosure

W.E.E. Eberhardt: Honoraria: Ad board -Roche (R), Pfizer (P), BI, Novartis (N), AstraZeneca (AZ), GSK, BMS, Amgen, Teva, MerckSerono (MS), Merck (M), Astellas, Eli Lilly (EL); educational lectures -R, P, BI, N, AZ, GSK, BMS, Amgen, MS, M, EL; funding clinical trial –EL; F.A. Shepherd: Frances A Shepherd participated on advisory boards for Roche/Astellas/OSI 1+ years ago which were compensated, and gave a compensated lecture for Roche 2+ years ago; J. Wang: Joe Wang is an employee of Astellas; J. Wu: Jun Wu is an employee of Astellas; S.C. Gill: Stanley C Gill is an employee of Astellas; K.K. Iwata: Kenneth K Iwata is an employee of Astellas; F.C. Richardson: Frank C Richardson works for FC Richardson Consulting LTC; J.D. Horan: Julie Horan is an employee of Novella Clinical (former OSI Pharmaceutical employee); M.A. Foley: Margaret A Foley is an employee of Astellas. All other authors have declared no conflicts of interest.