In EGFR mutant NSCLC, acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) inevitably occurs. To date, inconclusive results have been published or presented regarding the predictive/prognostic role of PDL1 expression in EGFR mutant NSCLC treated with TKIs.
A retrospective analysis of patients treated with first (Erlotinib/Gefitinib), second (Afatinib) and third generation (Osimertinib) EGFR-TKIs was conducted. The main objective was to evaluate the potential correlation between levels of PDL1 expression and anti-EGFR treatment efficacy in terms of overall survival (OS) and progression-free-survival (PFS).
Data from 171 patients (median age 69.0 years) who received EGFR TKIs were gathered. The most common EGFR alteration was ex19del (52.6%). 26 patients (15.2%) showed high PDL1 expression (≥50%). 105 patients (61.4%) were treated with Osimertinib, while 22.2%, 12.3% and 4.1% were treated with Gefitinib, Afatinib and Erlotinib, respectively. In the overall population, the objective response rate was 61%, mPFS 19.1 months (15.1–23.1) and 2-year OS 61.5%. Results of multivariate analysis are reported in the
Univariate HR (95% CI) | Multivariate HR (95% CI) | |
---|---|---|
ECOG PS | P < 0.0001 | P = 0.002 |
0 | 1.00 | 1.00 |
1 | 1.33 (0.80–2.21) | 1.60 (0.95–2.72) |
2–3 | 5.09 (2.70–9.60) | 3.73 (1.78–7.82) |
PDL1 | P = 0.03 | P = 0.073 |
<=49% | 1.00 | 1.00 |
>=50% | 1.87 (1.06–3.29) | 1.71 (0.95–3.08) |
Mutation | p = 0.11 | |
Esone 19 | 1.00 | |
Esone21 | 1.24 (0.77–2.00) | |
Number of met sites | P = 0.40 | |
1 | 1.00 | |
2 | 1.69 (0.71–4.03) | |
>=3 | 1.72 (0.78–3.79) | |
Surgery | P = 0.03 | P = 0.095 |
No | 1.00 | 1.00 |
Yes | 0.46 (0.23–0.93) | 0.54 (0.26–1.12) |
TKIs | P = 0.006 | P = 0.001 |
Gefitinib/Erlotinib | 1.00 | 1.00 |
Afatinib | 0.62 (0.31–1.26) | 0.48 (0.22–1.06) |
Osimertinib | 0.45 (0.27–0.73) | 0.36 (0.21–0.61) |
First-line | P < 0.0001 | P = 0.08 |
No | 1.00 | 1.00 |
Yes | 0.14 (0.06–0.35) | 0.39 (0.13–1.12) |
Our study supports the survival benefit of Osimertinib compared to first/second generation TKIs, regardless of PDL1 expression. A larger data collection is ongoing and updated results will be presented at the Conference.
The authors.
Has not received any funding.
E. Bria: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, MSD, Eli Lilly, Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche. S. Pilotto: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, AstraZeneca, Merck & Co., Roche, Amgen, Novartis; Financial Interests, Personal, Advisory Board: Merck & Co., Amgen, AstraZeneca, Novartis; Financial Interests, Personal, Expert Testimony: Takeda; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Roche. All other authors have declared no conflicts of interest.