Abstract 1158P
Background
In first line (L1) for EGFR-mutated (mEGFR) advanced NSCLC (aNSCLC), osimertinib (osi) has been the preferred option since 2018. First generation anti-EGFR TKI (1G) alone followed by osi, or 1G + anti-angiogenic or 1G + chemotherapy are other options. We aimed to assess the subgroups of patients (pts) that do not benefit from 1G alone compared with osimertinib L1 in mEGFR aNSCLC.
Methods
Retrospective international study including pts with mEGFR aNSCLC treated with either osi or the sequence of 1G followed by osi (seq group). Primary endpoint was the PFS of the global strategy (PFSglob) defined as the time between L1 start and progression after L2 treatment or death. Subgroups analyses included pts with high tumour burden (high-TM; > 3 metastatic sites and/or central nervous system (CNS) involvement), poor performance status (PS), and T790M negative (seq subgroup only).
Results
A total of 235 pts were included: 104 in the seq group, 118 in the osi L1 group. 15 had T790M negative at PD after 1G, they received osi as a therapeutic test. From these pts, 222 had an exon19 or 21 EGFR mut, 13 had uncommon mEGFR. Mean age was 65 years, 64% were female, and 60% never smokers. Pts from the osi L1 group had poorer PS (23% vs 10%), higher rate of co-mutations (23% vs 19%) and more CNS involvement (47% vs 19%). After a median (m) follow up of 30.6 months in the exon 19 and 21 population, mPFSglob was 27.4 mo (23.0-31.0) and mPFS L1 was 15.5mo (13.7-18.4) Table. The sequence was associated with shorter PFS L1 compared with osi L1 particularly in high-TM (10.5 mo vs 17.1 mo, p<0.0001); PFS was numerically shorter in poor PS (≥2) population (11.0 mo vs 15.6 mo, p=0.1). Table: 1158P
| Osimertinib L1 group | ORR L1 | PFS L1, 18mo rate (95%CI) | PFSglob, 36mo rate (95%CI) |
| Exon 19 and 21 mut (n=118) | 84.3% | 46.4% (37.0-58.1) | 36.8% (19.9-68.2) |
| CNS involvement (n=55) | 92.6% | 42.2% (28.3-62.7) | 20.6% (4.7-89.0) |
| Poor PS (n=23) | 90.5% | 46.4% (27.7-77.8) | 55.1% (35.5-85.5) |
| Sequence group | |||
| Exon 19 and 21 mut (n=104) | 87.4% | 41.8% (33.2-52.5) | 37.8% (29.1-49.1) |
| CNS involvement (n=20) | 90.0% | 25% (11.7-53.4) | 16.6% (5.2-53.0) |
| Poor PS (n=9) | 88.9% | 13.9% (2.3-83.6) | 0% |
| ORR L2 | PFS L1, 18mo rate (95%CI) | PFS L2, mo (95%CI) | |
| T790M analysis from the sequence group | |||
| T790M positive at L1 PD (n=82) | 63.2% | 39.0% (29.8-51.1) | 10.3 (8.8-14.1) |
| T790M negative at L1 PD (n=9) | 83.3% | 44.4% (21.4-92.3) | 12.8 (6.7-Not Reached) |
Conclusions
1G TKI followed by osi seemed to be detrimental compared with os L1 for pts with high-TM or poor PS mEGFR aNSCLC. In this population, the intensification of L1 treatment with osimertinib or a combination of 1G with anti-angiogenic or chemotherapy could be the better option in the first-line setting. Updated results will be presented at the congress.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Has not received any funding
Disclosure
E. Auclin: Financial Interests, Personal, Advisory Board: Sanofi, Amgen. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Other, Family member is an employee: AstraZeneca. M.T. Moran Bueno: Financial Interests, Personal, Advisory Board, Advisory Role: AstraZeneca, Boehringer Ingelheim, BMS; Financial Interests, Personal, Advisory Board, Advisory role: Roche. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda; Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI; Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS; Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen; Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. All other authors have declared no conflicts of interest.