Abstract 1811P
Background
Histological transformation of NSCLC is a rare mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Information about molecular features and treatment outcomes in these patients (pts) is limited, regarding small retrospective cohort studies or case reports.
Methods
EGFR-m patients referring to four Italian Centers were retrospectively evaluated. Clinical data and biological samples of pts undergoing histological transformation over the last five years were collected. Centralized molecular characterization by Next Generation Sequencing (NGS) analysis was performed in tissue (Oncomine Comprehensive Assay v3, Thermofisher) at baseline and at time of progression, in plasma (Avenio cfDNA expanded panel, Roche) at progression.
Results
Nineteen pts were identified: 13 (68%) small cell lung cancer (SCLC), 3 (16%) squamous cell carcinoma (SCC) and 3 (16%) sarcomatoid/pleomorphic phenotype. Clinical features are summarized in the table. Table: 1811P
| Features | Total (n=19) | SCLC (n=13) | SCC (n=3) | Sarcomatoid/pleomorphic phenotype (n=3) |
| Age Median (range) | 63 (39-80) | 63 (39-78) | 74 (47-76) | 56 (41-80) |
| Sex (%) Male Female | 8 (42) 11 (58) | 6 (46) 7 (54) | 0 3 (100) | 2 (67) 1 (33) |
| Smoking history (%) Never smoking Ever smoking | 10 (53) 9 (47) | 6 (46) 7 (54) | 3 (100) 0 | 1 (33) 2 (67) |
| EGFR mutation (%) exon 19 deletion exon 21 L858R | 13 (68) 6 (32) | 8 (62) 5 (38) | 3 (100) 0 | 2 (67) 1 (33) |
| 1st line EGFR-TKI (%) Erlotinib Gefitinib Afatinib Erlotinib + bevacizumab Osimertinib | 3 (16) 9 (47) 2 (11) 1 (5) 4 (21) | 2 (15) 5 (38) 2 (15) 1 (8) 3(23) | 1 (33) 2 (67) 0 0 0 | 0 2 (67) 0 0 1 (33) |
| 2nd line osimertinib | 11 (58) | 7 (54) | 3 (100) | 1 (33) |
The median time from diagnosis to histological transformation was 17.4 months (95% CI, 13.9 to 20.9) with a median overall survival of 32.2 months (95% CI, 24.6 to 39.8). At baseline TP53 mutation (mut) was found in 6 out of 9 cases (67%). At the time of histological transformation, tissue NGS analysis had been performed in 14 pts, the most common genetic alterations were: TP53 mut (6, 42%), MYC amplification (4, 28%), CDKN2A mut (2, 14%), with the persistence of activating EGFR mut in all cases. Plasma NGS analyses, performed in 9 pts, confirmed the presence of EGFR sensitizing mut, with T790M mut (2, 22%), TP53 mut (3, 33%), MET amplification (3, 33%), RB1 mut (2, 22%). Mean cell-free DNA concentration was 228 ng/ml.
Conclusions
Histological and molecular evaluations are complementary in studying EGFR-TKI acquired resistance. NGS analyses in plasma might correlate with the risk of histological transformation and open new treatment perspectives.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Bonanno: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Boehringer Ingelheim; Financial Interests, Personal, Other: MSD. M.L. Reale: Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. L. Righi: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. G. Pasello: Financial Interests, Personal, Other: Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Roche, Eli Lilly; Financial Interests, Personal, Advisory Role: AstraZeneca. P. Bironzo: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, BMS, Roche, MSD, AstraZeneca. V. Guarneri: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eli Lilly, MSD. P. Conte: Financial Interests, Personal, Other: Novartis, Lilly, AstraZeneca, Tesaro; Financial Interests, Personal, Other: BMS, Roche, Lilly, Novartis, AstraZeneca; Financial Interests, Institutional, Other: Novartis, Roche, Lilly, BMS, Merck-Serono. S. Novello: Financial Interests, Personal, Invited Speaker: Eli Lilly, MSD, Roche, BMS, Takeda, Pfizer, AstraZeneca, Boehringer Ingelheim. All other authors have declared no conflicts of interest.