96O - Determining the prevalence of EGFR mutations in Asian and Russian patients (pts) with advanced non-small-cell lung cancer (aNSCLC) of adenocarcinoma...

Date 16 April 2015
Event ELCC 2015
Session New treatment avenues
Topics Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Cancer Aetiology, Epidemiology, Prevention
Presenter Baohui Han
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors B. Han1, S. Tjulandin2, K. Hagiwara3, N. Normanno4, L. Wulandari5, L. Konstantin Konstantinovich6, A. Hudoyo7, M. Ratcliffe8, R. McCormack8, M. Reck9
  • 1Department Of Respiratory Medicine, Shanghai Chest Hospital, Jiao Tong University, 200030 - Shanghai/CN
  • 2Department Of Clinical Pharmacology And Chemotherapy, Russian Cancer Research Center, Moscow/RU
  • 3Department Of Respiratory Medicine, Saitama Medical University, Iruma-gun/JP
  • 4Cell Biology And Biotherapy Unit, Instituto Nazionale Tumori Fondazione Pascale, Naples/IT
  • 5Department Of Pulmonology, Dr Soetomo General Hospital, Surabaya/ID
  • 6Department Of Clinical Biotechnology, Russian Cancer Research Center, Moscow/RU
  • 7Department Of Pulmonology And Respiratory Medicine, University of Indonesia - Persahabatan Hospital, Jakarta/ID
  • 8Personalized Healthcare And Biomarkers, AstraZeneca, Macclesfield/UK
  • 9Department Of Thoracic Oncology, LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Centre for Lung Research (DZL), 22927 - Grosshansdorf/DE

Abstract

Aim/Background

IGNITE (a large, multinational, diagnostic, non-comparative, interventional study; NCT01788163) assessed EGFR mutation frequency in pts with aNSCLC of ADC/non-ADC histology.

Methods

Pts: local/metastatic aNSCLC (chemotherapy naïve, newly diagnosed/recurrent disease after resection; ineligible for curative treatment) from 90 centres in Asia Pacific/Russia. Primary endpoint: EGFR mutation frequency by histology (locally tested). Secondary endpoints: EGFR mutation status concordance between matched tissue/cytology and plasma (circulating-free tumour-derived DNA) samples (China/Korea/Russia/Taiwan only); correlation between mutation status and demographic/disease status; treatment decisions; EGFR testing practices.

Results

3382 pts enrolled; tissue/cytology evaluable (Asia/Russia): 2291/924; plasma evaluable: 1753/941; median mutation test turnaround: 6/9 days. Tissue/cytology EGFR mutation frequency (Asia/Russia): ADC: 49/18%; non-ADC: 14/4% (squamous cell carcinoma: 10/4%); plasma generally lower (Table). Mutation status concordance in 2581 matched samples: 81% (95% CI 79–82); test sensitivity: 47% (43–51); specificity: 96% (95–97); positive predictive value (PPV): 83% (79–86); negative PV: 80% (78–82). PPV in 946 samples tested with identical highly sensitive methods: 91%. Plasma test sensitivity varied by country (30–54%); PPV lower in Russia (39%) vs Asia (93%). Mutation frequency significantly correlated with: ADC; never-smokers; Asian pts; greater number of metastatic organs; females (tissue/cytology only); age ≥65 years (plasma only) (Table).

EGFR mutation frequency, n/N (%) First-line treatment choice (most common only; tissue/cytology, n/N (%)
Tissue/cytology Plasma
ADC non-ADC ADC non-ADC EGFR mutation-positive EGFR mutation-negative
Overall 952/2249 (42) 89/927 (10) 397/1814 (22) 60/854 (7) Gefitinib 323/895 (36) Cisplatin 636/1559 (41) Carboplatin 575/1559 (37)
Country
Asia Pacific 862/1749 (49) 74/525 (14) 342/1301 (26) 31/445 (7) Gefitinib 299/809 (37) Carboplatin 368/1004 (37) Cisplatin 350/1004 (35)
Russia 90/500 (18) 15/402 (4) 55/513 (11) 29/409 (7) Carboplatin 28/86 (33) Gefitinib 24/86 (28) Paclitaxel 18/86 (21) Etoposide 18/86 (21) Cisplatin 286/555 (52) Etoposide 226/555 (41)
Mutation subtype and country
Exon 19 Del only Asia Pacific 420/862 (49) 29/74 (39) 173/342 (51) 14/31 (45)
Russia 53/90 (59) 6/15 (40) 38/55 (69) 21/29 (72)
L858R only Asia Pacific 366/862 (42) 41/74 (55) 143/342 (42) 14/31 (45)
Russia 23/90 (26) 3/15 (20) 17/55 (31) 7/29 (24)
Exon 20 insertions only Asia Pacific 20/862 (2) 0/74 (0) 6/342 (2) 0/31 (0)
Russia 0/90 (0) 0/15 (0) 0/55 (0) 1/29 (3)
G719X only Asia Pacific 10/862 (1) 1/74 (1) 5/342 (1) 0/31 (0)
Russia 0/90 (0) 0/15 (0) 0/55 (0) 0/29 (0)
L861Q only Asia Pacific 11/862 (1) 1/74 (1) 4/342 (1) 1/31 (3)
Russia 0/90 (0) 2/15 (13) 0/55 (0) 0/29 (0)
Other rare mutations/double mutationsa Asia Pacific 35/862 (4) 2/74 (3) 11/342 (3) 2/31 (6)
Russia 14/90 (16) 4/15 (27) 0/55 (0) 1/29 (3)
Correlations between demographic/disease status and EGFR mutation status
Demographic / Disease status Tissue/cytology Plasma (China/Korea/Russia/Taiwan only)
% p-value OR 95% CI % p-value OR 95% CI
ADC vs non-ADC 42 vs 10 <0.0001 3.973 2.943-5.364 22 vs 7 0.0002 1.955 1.377-2.774
Asia Pacific v Russia 41 vs 12 <0.0001 3.929 2.977-5.151 21 vs 9 <0.0001 2.084 1.525-2.848
Never- vs ever-smoker 52 vs 19 <0.0001 2.515 1.957-3.233 26 vs 11 <0.0001 2.077 1.624-2.656
Females vs male 52 vs 23 0.0075 1.409 1.096-1.811 26 vs 13 N/A N/A N/A
Greater number of organs with metastases, % of patients with EGFR mutation-positive NSCLC with 1/2/3/ ≥ 4 metastatic organs 34/39/46/48 0.0909 1.086 0.987-1.195 15/22/30/42 <0.0001 1.386 1.242-1.546
≤65 vs ≥65 years old N/A N/A N/A N/A 19 vs 14 0.0009 1.561 1.201-2.028

aIncludes L858R/Exon 19 Deletion + any other mutations OR, odds ratio; N/A, not available

Mutation subtype and country
Exon 19 Del only Asia Pacific 420/862 (49) 29/74 (39) 173/342 (51) 14/31 (45)
Russia 53/90 (59) 6/15 (40) 38/55 (69) 21/29 (72)
L858R only Asia Pacific 366/862 (42) 41/74 (55) 143/342 (42) 14/31 (45)
Russia 23/90 (26) 3/15 (20) 17/55 (31) 7/29 (24)
Exon 20 insertions only Asia Pacific 20/862 (2) 0/74 (0) 6/342 (2) 0/31 (0)
Russia 0/90 (0) 0/15 (0) 0/55 (0) 1/29 (3)
G719X only Asia Pacific 10/862 (1) 1/74 (1) 5/342 (1) 0/31 (0)
Russia 0/90 (0) 0/15 (0) 0/55 (0) 0/29 (0)
L861Q only Asia Pacific 11/862 (1) 1/74 (1) 4/342 (1) 1/31 (3)
Russia 0/90 (0) 2/15 (13) 0/55 (0) 0/29 (0)
Other rare mutations/double mutationsa Asia Pacific 35/862 (4) 2/74 (3) 11/342 (3) 2/31 (6)
Russia 14/90 (16) 4/15 (27) 0/55 (0) 1/29 (3)
Correlations between demographic/disease status and EGFR mutation status
Demographic / Disease status Tissue/cytology Plasma (China/Korea/Russia/Taiwan only)
% p-value OR 95% CI % p-value OR 95% CI
ADC vs non-ADC 42 vs 10 <0.0001 3.973 2.943-5.364 22 vs 7 0.0002 1.955 1.377-2.774
Asia Pacific v Russia 41 vs 12 <0.0001 3.929 2.977-5.151 21 vs 9 <0.0001 2.084 1.525-2.848
Never- vs ever-smoker 52 vs 19 <0.0001 2.515 1.957-3.233 26 vs 11 <0.0001 2.077 1.624-2.656
Females vs male 52 vs 23 0.0075 1.409 1.096-1.811 26 vs 13 N/A N/A N/A
Greater number of organs with metastases, % of patients with EGFR mutation-positive NSCLC with 1/2/3/ ≥ 4 metastatic organs 34/39/46/48 0.0909 1.086 0.987-1.195 15/22/30/42 <0.0001 1.386 1.242-1.546
≤65 vs ≥65 years old N/A N/A N/A N/A 19 vs 14 0.0009 1.561 1.201-2.028

aIncludes L858R/Exon 19 Deletion + any other mutations OR, odds ratio; N/A, not available.

Conclusions

These real-world data suggest EGFR mutation frequency is higher in pts with aNSCLC of ADC vs non-ADC histology; yet mutations seen in non-ADC supports mutation testing in all pts. Plasma data will be discussed further in the presentation.

Clinical trial identification This study is available on clinicaltrials.gov (NCT01788163) with a first received date of February 7th 2013. No study results have yet been posted.

Disclosure

B. Han: Speakers bureau: Roche, AstraZeneca; Consultant: AstraZeneca, Pfizer

S. Tjulandin: Speakers bureau: AstraZeneca; Grants/research support: Celgene

K. Hagiwara: Speakers bureau–AstraZeneca, Pfizer, Chugai Pharmaceuticals; Patent: LSI Medience

N. Normanno: Grants/research support/consultant: AstraZeneca

L. Wulandari: Speakers bureau: AstraZeneca; Consultant: Boehringer Ingelheim

M. Ratcliffe and R. McCormack: Employee of AstraZeneca and holds shares in AstraZeneca

M. Reck: Speakers bureau: Hoffmann-La Roche, Lilly, BMS, AstraZeneca, Pfizer, Daiichi-Sankyo, Boehringer Ingelheim; Consultant: Hoffmann-La Roche, Lilly, BMS, AstraZeneca, Pfizer, Daiichi-Sankyo, Boehringer Ingelheim, MSD.

All other authors have declared no conflicts of interest.