1278P - ORIGEN: Multicenter study on the prevalence of EGFR gene mutations in patients with early-stage resectable non-small cell lung cancer in Spain

Background

The presence of EGFR mutations (EGFRm) has therapeutic implications in patients (pts) with non-squamous non-small cell lung cancer (NSCLC). In Spain, the frequency of EGFRm in pts with early stage resected NSCLC was not known. The aim of the study is to determine the prevalence and characteristics of EGFRm in pts with early stage surgically resected non-squamous NSCLC.

Methods

Multicenter observational study of adult pt with early-stage non-squamous NSCLC (IA-IIIB) candidates for surgical treatment. The study involved 21 centers in Spain. Pts were required to sign informed consent and to have formalin-fixed, paraffin-embedded samples. Analysis of EGFR mutational status was performed in each participating site using Biocartis solution (EGFR Idylla™) which recognizes 51 mutations in exons 18-21 in a single tissue section.

Results

One hundred seventy-two pts were analyzed, median age 67.5 years, 58% male, 31% current smokers and 52% former smokers. The predominant histology was adenocarcinoma (97%) and the most frequent stage was IA (47%). Pathological diagnosis was obtained by surgery in 53% of pts and by biopsy in 47% of pts. Only 4% of pts received neoadjuvant treatment and 21.7% received adjuvant treatment. The most frequent surgery was lobectomy (79%) followed by segmentectomy (15%), pneumonectomy (3%) and wedge resection (3%). All except 1 pt had R0 resection. The prevalence of EGFRm was 15% (25 pt), being deletions in exon 19 (52%) the most frequent alterations, followed by mutations in exon 21 (44%; 40% L858R) and exon 20 (4%). The prevalence of EGFRm by stage is shown in the table. Table: 1278P

Common EGFR mutations according to tumor stage

Conclusions

In this series of pts operated on for NSCLC, frequency of EGFR mutation was 15%, the most frequent being exon 19 deletions and the L858R mutation, in line with data reported in Spain in advanced NSCLC. These results reinforce the importance of performing EGFRm testing in early-stage NSCLC to identify pt candidates to adjuvant osimertinib.

Clinical trial identification

Editorial acknowledgement

Editorial assistance: Juan Luis Sanz (APICES).

Legal entity responsible for the study

AstraZeneca España.

Funding

AstraZeneca España.

Disclosure

E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Boehringer Ingelheim, Lilly, Janssen, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Boehringer Ingelheim, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen; Financial Interests, Personal and Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Personal and Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Funding, Merck Serono funded a clinical trial: Merck Serono; Non-Financial Interests, Advisory Role: Pfizer, Roche. C. Alvarez Fernandez: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck-Pfizer; Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Ipsen, AstraZeneca. H. Arasanz: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Clinical trial coordination: Ferrer Farma; Financial Interests, Personal, Other, Accommodation/travel expenses: Takeda, MSD, Angelini. M. Lázaro Quintela: Financial Interests, Personal, Invited Speaker: Roche, Eisai, Merck, Ipsen, Astellas, Novartis, Sanofi, Lilly; Financial Interests, Personal, Advisory Board: Astellas, Takeda, Pfizer, Ipsen. C. Teixido: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck Sharp & Dohme, Roche Farma, Diaceutics, Pfizer, Janssen Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Novartis. V. Calvo de Juan: Financial Interests, Personal, Speaker’s Bureau: Roche, BMS, AstraZeneca, Takeda, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: Roche, Amgen, Sanofi, BMS; Financial Interests, Personal, Other, Support for attending meeting and/or travel: Takeda, Roche. R.M. Alvarez: Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board: Boehringer, Novartis, Roche; Financial Interests, Personal, Other, conference registration: MSD Oncology; Financial Interests, Institutional, Coordinating PI: Roche; Financial Interests, Personal and Institutional, Coordinating PI: Janssen Oncology, Rain Therapeutics, Boehringer, Cebiotex, Novartis. J. Baena Espinar: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, BMS; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Advisory Role: Roche. J. Valdivia-Bautista: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, MSD; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre; Financial Interests, Personal, Other, Consulting: Sanofi. E. Arriola: Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, Lilly; Financial Interests, Personal, Invited Speaker: Takeda, MSD, AstraZeneca, BMS, Thermo Fisher Scientific, Guardant Health, Pfizer; Financial Interests, Personal, Other, Co-founder: Trialing Health; Financial Interests, Institutional, Research Grant: AstraZeneca. R. Lastra: Financial Interests, Personal, Other, Travel sponsor: Takeda; Financial Interests, Personal, Invited Speaker: ICAPEM, AstraZeneca, Roche, MSD. R. Bernabe Caro: Financial Interests, Personal, Research Funding: Roche; Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Amgen, Pfizer, Sanofi, Takeda, BMS; Financial Interests, Personal, Advisory Board: Roche, Sanofi, MSD, AstraZeneca, BMS. C. Camacho: Financial Interests, Personal, Invited Speaker: Lilly, AstraZeneca, Roche. T. Garcia Manrique: Financial Interests, Personal, Invited Speaker, Taller formativo MSD: MSD; Financial Interests, Personal, Advisory Board, Taller organizado por la sociedad española de nefrología: VIFOR; Financial Interests, Personal, Invited Speaker, Experiencia en combinaciones inmunoterapia en primea línea de cancer de pulmon metastásico: Bristol Myers Squibb; Non-Financial Interests, Principal Investigator, A Randomized, Double-Blind, Adaptive, Phase II/III Study of GSK3359609 in Combination With Pembrolizumab and 5FU-Platinum Chemotherapy Versus Placebo in Combination With Pembrolizumab Plus 5FU-Platinum Chemotherapy for First-Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: GSK; Non-Financial Interests, Principal Investigator, A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma.: Gilead; Non-Financial Interests, Principal Investigator, A Randomized, Double-Blind, Phase 3 Study of MK-7684A Plus Chemotherapy Versus Pembrolizumab Plus Chemo therapy as First Line Treatment for Participants With Metastatic Non-Small Cell Lung Cancer. (MK-7684A-007/KEYVIBE-007).: Merck Sharp & Dohme LLC; Non-Financial Interests, Principal Investigator, Pembrolizumab/Vibostolimab (MK-7684A) or Atezolizumab in Combination With Chemotherapy inFirst Line Treatment of Extensive-Stage Small Cell Lung Cancer (MK-7684A-008, KEYVIBE-008).: Merck Sharp & Dohme LLC; Non-Financial Interests, Principal Investigator, A Randomized, Double-blinded, Phase III Study of Atezolizumab Versus Placebo in Patients With Late Relapse of Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Treated by Platinum based Chemotherapy and Bevacizumab: Roche; Non-Financial Interests, Principal Investigator, Phase 2 Multicenter, Open-Label Study With a Randomized Control Arm of the Efficacy, Safety,and Pharmacokinetics of Intravenously Infused Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme (WHO Grade IV) After Failure of Standard First Line Therapy.: CNS Pharmaceuticals; Non-Financial Interests, Principal Investigator, A Phase 1, Open-Label, First-in-Human Study to Evaluate the Safety and Anti-tumour Activity ofFS222, a CD137/PD-L1 Bispecific Antibody, in Subjects With Advanced Malignancies: F-star Therapeutics Limited; Non-Financial Interests, Other, A Phase I, Open-Label Study of GSK1795091 Administered in Combination With Immunotherapies in Participants With Advanced Solid Tumors.: GSK; Non-Financial Interests, Other, A Phase I Open Label Study of GSK3359609 Administered Alone and in Combination WithAnticancer Agents in Subjects With Selected Advanced Solid Tumors.: GSK; Non-Financial Interests, Other, Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFRAberrations: Taiho Oncology, Inc.; Non-Financial Interests, Other, A Phase 1b Study to Assess the Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Subjects With Locally Advanced or Metastatic Solid Tumors: BeiGene; Non-Financial Interests, Other, A Phase 2 Trial of Pembrolizumab (MK-3475) in Combination With Platinum Doublet Chemotherapy and Radiotherapy for Participants With Unresectable, Locally Advanced Stage III Non-Small Cell Lung Cancer (NSCLC) (KEYNOTE-799): Merck Sharp & Dohme LLC; Non-Financial Interests, Other, An Exploratory Study of the Biologic Effects and Biomarkers of Nivolumab in Combination With Ipilimumab in Subjects With Treatment-Naive Stage IV or Recurrent Non-Small Cell Lung Cancer(NSCLC). Phase 2.: Bristol Myers Squibb; Non-Financial Interests, Other, A Multicentre, Open-label, Single-arm, Molecular Profiling Study of Patients With EGFR Mutation positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib. Phase 2: AstraZeneca; Non-Financial Interests, Other, A Phase IIa, Single-arm, Multicenter Study to Investigate the Clinical Activity and Safety ofAvelumab in Combination With Cetuximab Plus Gemcitabine and Cisplatin in Participants With Advanced Squamous NSCLC: Merck Serono; Non-Financial Interests, Other, Treatment Plan CINC280A02001M to Provide Access to Capmatinib, for MET Exon 14 Skipping Non-Small Cell Lung Cancer (NSCLC): Novartis Pharmaceuticals; Non-Financial Interests, Other, An Open Label Phase II Study of Tipifarnib in Advanced Squamous Non-small Cell Lung Cancer With HRAS Mutations. [NCT03496766]: Spanish Lung Cancer Group; Non-Financial Interests, Other, A Phase II, Open-Label, Multi-Arm Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer. [NCT02937818]: AstraZeneca; Non-Financial Interests, Other, A Randomized, Phase 3 Trial With Anti-PD-1 Monoclonal Antibody Pembrolizumab (MK-3475)Versus Placebo for Patients With Early Stage NSCLC After Resection and Completion of Standard Adjuvant Therapy (PEARLS): Merck Sharp & Dohme LLC; Non-Financial Interests, Other, A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutantNon-small Cell Lung Cancer: Pfizer; Non-Financial Interests, Other, A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy.: Roche; Non-Financial Interests, Principal Investigator, An Adaptive Phase III, Multicenter, Randomized, Open-Label, Controlled Study of M7824(Bintrafusp Alfa) Versus Pembrolizumab as a First-line Treatment in Patients With PD-L1Expressing Advanced Non-small Cell Lung Cancer. [: Merck Serono; Non-Financial Interests, Other, A phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, International Study of Osimertinib as Maintenance Therapy in Patients With Locally Advanced, Unresectable EGFR Mutation-positive Non-Small Cell Lung Cancer (Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-based Chemoradiation Therapy (LAURA): AstraZeneca; Non-Financial Interests, Other, A Phase 3 Study of Pembrolizumab in Combination With Carboplatin/Taxane (Paclitaxel or Nabpaclitaxel)Followed by Pembrolizumab With or Without Maintenance Olaparib in the First-lineTreatment of Metastatic Squamous Non-small Cell Lung Cancer (NSCLC): Merck Sharp & Dohme LLC. G.J. Marquez: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. All other authors have declared no conflicts of interest.