Osimertinib (Osi) is an EGFR-TKI that potently inhibits both EGFR-sensitizing and EGFR T790M resistance mutations in non-small cell lung cancer (NSCLC). Identification of oligo-progression (PD) on Osi may allow local treatment and continuation of Osi. Metastatic patterns at the time of acquired resistance to Osi are poorly understood.
We retrospectively analyzed 50 pre-treated T790M+ NSCLC patients who received Osi at 7 Swiss centers. Oligo-PD was defined as PD in ≤ 5 lesions. Archived pre-treatment and fresh biopsies at PD were analyzed for mutational profiling.
Median age was 62 years (range: 37-89), 64% females, 86% had a PS ≤ 1, 54%/13% were never/current smokers. Patients had one (44%), two (34%) or more (22%) prior treatment lines. At diagnosis, patients had EGFR exon 19 deletion (74%), L858R exon 21 mutation (24%) and concomitant exon 18/ exon 20 mutation (2%). Before Osi start, T790M was detected in blood (28%) or tumor tissue (72%). Median follow-up was 15.3 (IQR: 8.6-21.6) months. Overall response rate was 83%, median progression-free survival 15.1 months (IQR: 6.4-20.1), median overall survival 25.1 months (IQR: 16.7-not reached [NR]) and median treatment duration 18.1 months (IQR: 10.1-23.5). At data cut off, PD had occurred in 26 patients (52%). There were 73% oligo- vs. 27% systemic PD. Median treatment duration in patients with oligo-PD was 19.6 vs 6.5 months if systemic PD. The number of progressive lesions in oligo-PD patients were 1 (32%), 2 (37%), 3 (26%), and 5 (5%). Main sites of PD were lung (n = 14), bone (n = 10), lymph nodes (n = 6), liver and pleura (n = 5 each), and brain (n = 4). 12 patients with oligo-PD continued treatment with Osi beyond progression, ten of them after local therapy (8x radiotherapy, 2x surgery). Median time of treatment beyond PD was 10.7 months in patients with oligo-PD (IQR: 5.7-NR). Analyses of pretreatment and post-PD tumor tissue from a subset of patients will be presented.
In patients with acquired resistance to Osi, we observed a high rate of extracranial oligo-PD. Outcomes of patients with oligo-PD were favorable with the majority continuing Osi in addition to local therapy, supporting the concept of Osi treatment beyond progression in combination with local therapy of progressing lesions.
Clinical trial identification
Legal entity responsible for the study
Kantonsspital St. Gallen.
Institutional funding from AstraZeneca for molecular analysis.
S. Schmid: Research funding (Institutional): AstraZeneca, BMS Advisory (Institutional): Boehringer Ingelheim. S.I. Rothschild: Consulting/Advisory Role (Institutional): BMS, AstraZeneca, Lilly, Boehringer Ingelheim, Eisai, Roche, Novartis, Merck Serono, MSD Oncology, Astellas Pharma, Bayer, Pfizer, Takeda; Research funding (institutional): Boehringer Ingelheim, AstraZeneca, BMS, Eisai, Merck Serono; Travel, Accommodation: Roche, Lilly, BMS, AstraZeneca, Merck Sharp and Dohme, Amgen. W-D. Janthur: Advisory boards: Roche, Boehringer Ingelheim, Takeda, MSD. M. Früh: Advisory Board AstraZeneca. All other authors have declared no conflicts of interest.