S Schmid1, D Klingbiel2, S Aeppli3, C Britschgi4, O Gautschi5, M Pless6, S Rothschild7, L Wannesson8, W Janthur9, D Foerbs10, I Demmer10, W Jochum10, M Früh3. 1. Department of Oncology/Haematology, Cantonal Hospital St. Gallen, University of Bern Switzerland, Switzerland. Electronic address: Sabine.schmid@kssg.ch. 2. SAKK, Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland. 3. Department of Oncology/Haematology, Cantonal Hospital St. Gallen, University of Bern Switzerland, Switzerland. 4. Department of Hematology and Oncology, University Hospital Zürich, Switzerland. 5. Department of Oncology, Cantonal Hospital Lucerne, Switzerland. 6. Department of Oncology, Cantonal Hospital Winterthur, Switzerland. 7. Department of Oncology, University Hospital Basel, Switzerland. 8. Istituto Oncologico della Svizzera Italiana, Ospedale Regionale di Bellinzona e Valli, Switzerland. 9. Department of Oncology, Cantonal Hospital Aarau, Switzerland. 10. Institute of Pathology, Cantonal Hospital St. Gallen, Switzerland.
Abstract
INTRODUCTION: Osimertinib is an EGFR tyrosine kinase inhibitor (TKI) with antitumor activity in non-small cell lung cancer (NSCLC) with EGFR T790 M mutations. The incidence of oligo-progression (PD) on osimertinib is unknown. METHODS: We retrospectively analyzed 50 pre-treated EGFR T790M-positive NSCLC patients treated with osimertinib at seven Swiss centers. Oligo-PD was defined as PD in ≤ 5 lesions. Mutational profiling of pre- and post-osimertinib tumor samples was performed. RESULTS: Median age was 62 years (37-89), 64% were females, 86% had a PS ≤ 1, 54%/13% were never/current smokers. Median follow-up was 15.3 (IQR: 8.6-21.6) months. Overall response rate was 80%, median progression-free survival 12.1 months (95% CI 8.3-18.3), median overall survival 28 months (95% CI 20.2-not reached [NR]) and median treatment duration 18.8 months (95%CI 16-8-NR). PD occurred in 36 patients (72%). 73% had oligo-PD. Median osimertinib treatment duration in patients with oligo-PD was 19.6 vs. 7 months if systemic PD (p = 0.007). The number of progressive lesions in patients with oligo-PD was 1 (27%), 2 (35%) and 3-5 (39%). Sites of PD included lungs (56%), bones (44%), and brain (17%). Sixteen patients with oligo-PD continued treatment with osimertinib for a median of 6.7 months beyond PD. Thirteen received local ablative treatment (LAT). In pre- and post-PD tumor tissue multiple molecular alterations were detected. CONCLUSION: In patients with acquired resistance to osimertinib, we observed a high rate (73%) of oligo-PD. Outcomes of patients receiving LAT were favorable, supporting the concept of osimertinib treatment beyond progression in combination with LAT of progressing lesions.
INTRODUCTION: Osimertinib is an EGFR tyrosine kinase inhibitor (TKI) with antitumor activity in non-small cell lung cancer (NSCLC) with EGFR T790 M mutations. The incidence of oligo-progression (PD) on osimertinib is unknown. METHODS: We retrospectively analyzed 50 pre-treated EGFR T790M-positive NSCLC patients treated with osimertinib at seven Swiss centers. Oligo-PD was defined as PD in ≤ 5 lesions. Mutational profiling of pre- and post-osimertinib tumor samples was performed. RESULTS: Median age was 62 years (37-89), 64% were females, 86% had a PS ≤ 1, 54%/13% were never/current smokers. Median follow-up was 15.3 (IQR: 8.6-21.6) months. Overall response rate was 80%, median progression-free survival 12.1 months (95% CI 8.3-18.3), median overall survival 28 months (95% CI 20.2-not reached [NR]) and median treatment duration 18.8 months (95%CI 16-8-NR). PD occurred in 36 patients (72%). 73% had oligo-PD. Median osimertinib treatment duration in patients with oligo-PD was 19.6 vs. 7 months if systemic PD (p = 0.007). The number of progressive lesions in patients with oligo-PD was 1 (27%), 2 (35%) and 3-5 (39%). Sites of PD included lungs (56%), bones (44%), and brain (17%). Sixteen patients with oligo-PD continued treatment with osimertinib for a median of 6.7 months beyond PD. Thirteen received local ablative treatment (LAT). In pre- and post-PD tumor tissue multiple molecular alterations were detected. CONCLUSION: In patients with acquired resistance to osimertinib, we observed a high rate (73%) of oligo-PD. Outcomes of patients receiving LAT were favorable, supporting the concept of osimertinib treatment beyond progression in combination with LAT of progressing lesions.
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