Oliver Gautschi1, Nicholas Mach2, Sacha I Rothschild3, Qiyu Li4, Rolf A Stahel5, Alfred Zippelius3, Richard Cathomas6, Martin Früh7, Daniel C Betticher8, Solange Peters9, Daniel Rauch10, Jonas Feilchenfeldt11, Lukas Bubendorf12, Spasenija Savic12, Rolf Jaggi13, Elisabeth Oppliger Leibundgut14, Carlo Largiadèr15, Martin Brutsche16, Christiane Pilop4, Lukas Stalder4, Miklos Pless17, Adrian F Ochsenbein18. 1. Medical Oncology, Cantonal Hospital Luzern, Luzern, Switzerland. Electronic address: oliver.gautschi@luks.ch. 2. Clinical Research Unit of the Dr. Dubois-Ferrière Dinu Lipatti Foundation, Oncology Center, Geneva University Hospital, Geneva, Switzerland. 3. Medical Oncology, University Hospital Basel, Basel, Switzerland. 4. SAKK Coordinating Center, Bern, Switzerland. 5. Medical Oncology, University Hospital Zurich, Zurich, Switzerland. 6. Medical Oncology, Cantonal Hospital Graubünden, Chur, Switzerland. 7. Medical Oncology, Cantonal Hospital St Gallen, St Gallen, Switzerland. 8. Medical Oncology, Cantonal Hospital Fribourg, Fribourg, Switzerland. 9. Cancer Center, University Hospital Lausanne, Lausanne, Switzerland. 10. Medical Oncology, Cantonal Hospital Thun, Thun, Switzerland. 11. Medical Oncology, Cantonal Hospital Valais, Sion, Switzerland. 12. Institute of Pathology, University Hospital Basel, Basel, Switzerland. 13. Department of Clinical Research, University of Bern, Bern, Switzerland. 14. Department of Hematology, University Hospital Bern, Bern, Switzerland. 15. Laboratory of Clinical Chemistry, University Hospital Bern, Bern, Switzerland. 16. Pulmonology, Cantonal Hospital St Gallen, St Gallen, Switzerland. 17. Medical Oncology, Cantonal Hospital Winterthur, Winterthur, Switzerland. 18. Medical Oncology, University Hospital Bern, Bern, Switzerland.
Abstract
OBJECTIVE: The goal was to demonstrate that tailored therapy, according to tumor histology and epidermal growth factor receptor (EGFR) mutation status, and the introduction of novel drug combinations in the treatment of advanced non-small-cell lung cancer are promising for further investigation. METHODS: We conducted a multicenter phase II trial with mandatory EGFR testing and 2 strata. Patients with EGFR wild type received 4 cycles of bevacizumab, pemetrexed, and cisplatin, followed by maintenance with bevacizumab and pemetrexed until progression. Patients with EGFR mutations received bevacizumab and erlotinib until progression. Patients had computed tomography scans every 6 weeks and repeat biopsy at progression. The primary end point was progression-free survival (PFS) ≥ 35% at 6 months in stratum EGFR wild type; 77 patients were required to reach a power of 90% with an alpha of 5%. Secondary end points were median PFS, overall survival, best overall response rate (ORR), and tolerability. Further biomarkers and biopsy at progression were also evaluated. RESULTS: A total of 77 evaluable patients with EGFR wild type received an average of 9 cycles (range, 1-25). PFS at 6 months was 45.5%, median PFS was 6.9 months, overall survival was 12.1 months, and ORR was 62%. Kirsten rat sarcoma oncogene mutations and circulating vascular endothelial growth factor negatively correlated with survival, but thymidylate synthase expression did not. A total of 20 patients with EGFR mutations received an average of 16 cycles. PFS at 6 months was 70%, median PFS was 14 months, and ORR was 70%. Biopsy at progression was safe and successful in 71% of the cases. CONCLUSIONS: Both combination therapies were promising for further studies. Biopsy at progression was feasible and will be part of future SAKK studies to investigate molecular mechanisms of resistance.
OBJECTIVE: The goal was to demonstrate that tailored therapy, according to tumor histology and epidermal growth factor receptor (EGFR) mutation status, and the introduction of novel drug combinations in the treatment of advanced non-small-cell lung cancer are promising for further investigation. METHODS: We conducted a multicenter phase II trial with mandatory EGFR testing and 2 strata. Patients with EGFR wild type received 4 cycles of bevacizumab, pemetrexed, and cisplatin, followed by maintenance with bevacizumab and pemetrexed until progression. Patients with EGFR mutations received bevacizumab and erlotinib until progression. Patients had computed tomography scans every 6 weeks and repeat biopsy at progression. The primary end point was progression-free survival (PFS) ≥ 35% at 6 months in stratum EGFR wild type; 77 patients were required to reach a power of 90% with an alpha of 5%. Secondary end points were median PFS, overall survival, best overall response rate (ORR), and tolerability. Further biomarkers and biopsy at progression were also evaluated. RESULTS: A total of 77 evaluable patients with EGFR wild type received an average of 9 cycles (range, 1-25). PFS at 6 months was 45.5%, median PFS was 6.9 months, overall survival was 12.1 months, and ORR was 62%. Kirsten ratsarcoma oncogene mutations and circulating vascular endothelial growth factor negatively correlated with survival, but thymidylate synthase expression did not. A total of 20 patients with EGFR mutations received an average of 16 cycles. PFS at 6 months was 70%, median PFS was 14 months, and ORR was 70%. Biopsy at progression was safe and successful in 71% of the cases. CONCLUSIONS: Both combination therapies were promising for further studies. Biopsy at progression was feasible and will be part of future SAKK studies to investigate molecular mechanisms of resistance.
Authors: Ursina B M Begré; Markus Jörger; Stefan Aebi; Ursula Amstutz; Carlo R Largiadèr Journal: Front Pharmacol Date: 2022-05-18 Impact factor: 5.988
Authors: Yang Liu; Zhi-Cheng Xiong; Xin Sun; Li Sun; Shu-Ling Zhang; Jie-Tao Ma; Cheng-Bo Han Journal: Transl Cancer Res Date: 2019-09 Impact factor: 1.241