Abstract 23P
Background
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.
Methods
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).
Results
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 table. Patients with PDL1 <50% showed mPFS of 15.4 (9.3–21.5) versus 23.6 months (18.6–28.6) with first/second and third generation TKIs, respectively (p = 0.018). Patients with PDL1 ≥50% showed mPFS of 8.0 months (3.1–12.8) versus 10.2 months (0–30.5) with first/second and third generation TKIs, respectively (p = 0.03). In the high PDL1 subgroup, a significant difference in OS was observed (mOS 24.9 versus 31.3 months with first/second versus third generation TKIs; p = 0.030). No statistically significant differences were reported when the analysis was limited to the first-line setting.
Table: 23P| 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) |
Conclusions
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.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
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.