ESMO Preceptorship Programme Colorectal Cancer– Valencia – 12-13 May 2017 Dirk Arnold Instituto CUF de Oncologia, Lisbon, Portugal A 68 year old…..former teacher....
ESMO Preceptorship Programme Colorectal Cancer– Valencia – 12-13 May 2017 Dirk Arnold Instituto CUF de Oncologia, Lisbon, Portugal A 68 year old…..former teacher....
Disclosures • Participate on Advisory Board with: Bayer, Merck, Roche, Lilly, sanofi, Servier, Sirtex, Terumo • Speaker and Chairman for educational events with: Bayer, Merck, Lilly, Servier, Terumo • Investigator and researcher in data generating activities, (partly) supported and sponsored by Bayer, Roche, Mologen
Patient profile and presentation Patient details • 68-year-old woman • Former teacher • Single • Enjoys hiking Patient presented with • Constipation and weight loss • ECOG PS 0 Colonoscopy/biopsy • Adenocarcinoma in right transversal colon Laboratory tests • CEA: 168ng/mL CT scans • no distant metastases
Initial management: Surgical procedure • Tumor near right flexure � extended right hemicolectomy • Pathology: • pT3 N1 M0 • 2 of 19 lymph nodes positive • RAS wild type • Post-operative CEA: 15 ng/ml
Initial management: Surgical procedure • Tumor near right flexure � extended right hemicolectomy • Pathology: • pT3 N1 M0 • 2 of 19 lymph nodes positive • RAS wild type • Post-operative CEA: 15 ng/ml • Adjuvant treatment refused
At 6 month follow-up visit: CT scan
Where are we now? • Tumor near right flexure � extended right hemicolectomy • Pathology: • pT3 N1 M0 • 2 of 19 lymph nodes positive • RAS wild type • Post-operative CEA: 15 ng/ml • Adjuvant treatment refused
Where are we now? • Tumor near right flexure � extended right hemicolectomy • Pathology: • pT3 N1 M0 • 2 of 19 lymph nodes positive • RAS wild type • Post-operative CEA: 15 ng/ml • Adjuvant treatment refused • Now relapsed within 6 months
Where are we now? • Tumor near right flexure � extended right hemicolectomy • Pathology: • pT3 N1 M0 • 2 of 19 lymph nodes positive • RAS wild type • Post-operative CEA: 15 ng/ml • Adjuvant treatment refused • Now relapsed within 6 months • Hepatic, nodal and (suspected) peritoneal disease
Where are we now? • Tumor near right flexure � extended right hemicolectomy • Pathology: • pT3 N1 M0 • 2 of 19 lymph nodes positive • RAS wild type • Post-operative CEA: 15 ng/ml • Adjuvant treatment refused • Now relapsed within 6 months • Hepatic, nodal and (suspected) peritoneal disease • CEA 223 mg/nl
Where are we now? • Tumor near right flexure � extended right hemicolectomy • Pathology: • pT3 N1 M0 • 2 of 19 lymph nodes positive • RAS wild type • Post-operative CEA: 15 ng/ml • Adjuvant treatment refused • Now relapsed within 6 months • Hepatic, nodal and (suspected) peritoneal disease • CEA 223 mg/nl • No symptoms, medically fit
Key questions in management of our patient • What is our treatment goal? • „Cure“ � „palliative“ � oligometastatic stabilization“? • Which treatment intensity is needed? • No treatment (yet) � mono � doublet � triplet • What is the best regimen then ?? • Which chemotherapy? Which monoclonal antibody?
Key questions in management of our patient • What is our treatment goal? • „Cure“ � „palliative“ � oligometastatic stabilization“? • Which treatment intensity is needed? • No treatment (yet) � mono � doublet � triplet • What is the best regimen then ?? • Which chemotherapy? Which monoclonal antibody?
Key questions in management of our patient • What is our treatment goal? • „Cure“ � „palliative“ � oligometastatic stabilization“? • Which treatment intensity is needed? • No treatment (yet) � mono � doublet � triplet • What is the best regimen then ?? • Which chemotherapy? Which monoclonal antibody?
Key questions in management of our patient • What is our treatment goal? • „Cure“ � „palliative“ � oligometastatic stabilization“? • Which treatment intensity is needed? • No treatment (yet) � mono � doublet � triplet • What is the best regimen then ?? • Which chemotherapy? Which monoclonal antibody?
Memory: Some factors that may impact on our decision making • Relapse within 6 months • Primary at right flexure, UICC III • RAS wild type • Medically fit, no comorbidities • Adjuvant treatment refused • Liver mets and lymph nodes enlarged • Suspected peritoneal carcinomatosis
Memory: Some factors that may impact on our decision making • Relapse within 6 months • Primary at right flexure, UICC III • RAS wild type • Medically fit, no comorbidities • Adjuvant treatment refused • Liver mets and lymph nodes enlarged • Suspected peritoneal carcinomatosis • BRAF wild type
Start with FOLFOX/bevacizumab CT scans at 5.5 months • “Minor response” (stable disease according to RECIST) • No tumour-related symptoms • CEA normalized
Treatment decision after 5.5 months FOLFOX-bevacizumab and mild neuropathy (2°) What change would suggest? – Continue bevacizumab plus 5-FU/LV and discontinue oxaliplatin – Continue bevacizumab alone and discontinue FOLFOX – Switch from FOLFOX to FOLFIRI – Stop all treatment – Role of local treatment (liver)?
Treatment decision after 5.5 months FOLFOX-bevacizumab and mild neuropathy (2°) What change would suggest? – Continue bevacizumab plus 5-FU/LV and discontinue oxaliplatin – Continue bevacizumab alone and discontinue FOLFOX – Switch from FOLFOX to FOLFIRI – Stop all treatment – Role of local treatment (liver)?
Treatment decision after 5.5 months FOLFOX-bevacizumab and mild neuropathy (2°) What change would suggest? – Continue bevacizumab plus 5-FU/LV and discontinue oxaliplatin – Continue bevacizumab alone and discontinue FOLFOX – Switch from FOLFOX to FOLFIRI – Stop all treatment – Role of local treatment (liver)?
De-escalation maintenance strategies: Progression-free survival (PFS) AIO: Arnold, et al. ASCO 2014; Hegewisch-Becker et al., Lancet Oncol 2015 DCCG: Koopman, et al., ASCO 2014; Simkens et al., Lancet 2015
De-escalation maintenance strategies: Overall survival (OS) Median OS: 18.1 vs. 21.6 mos (+3.5 mos.) HR nihil vs. FP/Bev: exploratory, n.s. HR nihil vs. FP/Bev: 0.83 ; p=0.06 AIO: Arnold, et al. ASCO 2014; Hegewisch-Becker et al., Lancet Oncol 2015 DCCG: Koopman, et al., ASCO 2014; Simkens et al., Lancet 2015
Maintenance with Bevacizumab and/without FP: Combined analysis; update PFS OS Arnold et al., ASCO 2016 (oral presentation) Stein et al., Clin Colorectal Cancer 2016
AIO 0207: Quality of life analyses 40. 40. FP/Bev. 30. 30. Bev. 20. 20. Ø.Tx. 10. 10. 0. 0. Patientenanzahl in % Patientenanzahl in % @ wk 24: @ wk 24: (Mittelwert 1 ) (Mittelwert 1 ) % of patients % of patients with at least 10 IP with at least 10 IP „overall HRQoL“ „overall HRQoL“ improvement deterioration Quidde et al., Ann Oncol 2016
Thank you for listening Dirk Arnold Instituto CUF de Oncologia Lisboa, Portugal dirk.arnold@jmellosaude.pt
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