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A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study
Annals of Oncology
abstracts
663TiP
A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study
M.A. Barbera1, J. Corbelli1, G. Papiani1, E. Grassi2, G. Ugolini3, I. Montroni3, M. Di Bartolomeo4, S. Cascinu5, M. Marzola6, A. Bonetti7, G.L. Frassineti8, O. Nanni9, D. Zattoni3, F. Ghignone3, G. Taffurelli3, C. Pinto10, C. Carli Moretti11, G. Rossi12, S. Palazzi13, S. Tamberi14 1 Medical Oncology, Infermi Hospital - Faenza, Faenza, Italy, 2Department of Experimental, Diagnostic and Specialty Medicine - Dimes, AOU Policlinico S. OrsolaMalpighi, Bologna, Italy, 3Surgery Unit, Infermi Hospital - Faenza, Faenza, Italy, 4 Medical Oncology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 5Oncology, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy, 6Medical Oncology, Sant’Anna Hospital Cona-University of Ferrara, Cona, Italy, 7 Oncology, Ospedale Mater Salutis di Legnago, Legnago, Italy, 8Oncology, Istituto a Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, Italy, 9Unit di Biostatistica e Sperimentazioni Cliniche, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy, 10Clinical Canncer Center, Medical Oncology Unit, Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy, 11 Radiology Unit, Infermi Hospital - Faenza, Faenza, Italy, 12Pathology Unit, Ravenna Hospital, Ravenna, Italy, 13Radiotherapy Unit, Ravenna Hospital, Ravenna, Italy, 14 Medical Oncology, Infermi Hospital - Faenza, Faenza, Ravenna, Italy Background: The standard treatment for cT3-4 N0-1 rectal cancer is preoperative chemo-radiation therapy (CT/RT). The combination of capecitabine plus long course
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz246 | v249
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz246.140/5578202/ by guest on 07 October 2019
radiotherapy (RT) is standard therapy in locally advanced rectal cancer. Pathologic Complete remission (pCR) can be considered as surrogate end point of efficacy of treatment in terms of disease free survival (DFS). Clinical complete remission (cCR) is an important endpoint for “wait and see” strategy. In the PACIFIC trial in non-small cell lung cancer the patients were treated with durvalumab maintenance after CT/RT with advantage in progression free survival. “Abscopal effect” is proposed as mediator of systemic effects after localized RT. Preclinical data points heavily toward a strong synergy between RT and immune treatments. Recent reports already illustrate that such a systemic effect of RT is possible when enhanced by targeted immune treatments. Trial design: This is a prospective phase II, open label, single arm, multi-centre study to evaluate, in patients with operable rectal cancer, activity of an innovative sequence: standard concomitant CT/RT therapy with 825 mg/m2 twice daily capecitabine every day and 5040 cGy radiotherapy for 5 days per week for 5 weeks followed by 1500 mg Q4W durvalumab for 3 administration. After 9-10 weeks from neoadjuvant therapy will be performed re-staging with CT and MRI scan. Surgery will be performed at week 10-12 from the end of CT/RT. Primary Objective: pCR rate, defined as a TRG 3-4 according to DWORAK criteria. Secondary Objectives: Safety of treatment with durvalumab; cCR rate after durvalumab treatment before surgery and DFS. cCR will be evaluated with clinical, endoscopic and radiological assessment to look for evidence of residual disease. DFS will be evaluated during a follow up of 5 years. Exploratory Objective: Biological translational analysis of tumor biomarkers will be performed on the endoscopy biopsy done at the diagnosis and on the biopsy performed after the CT/ RT prior to treatment with durvavalumab. We have planned to enlist 60 patients in 7 centers with an enrollment period of 12 months, already underway. Clinical trial identification: 2018-004758-39. Legal entity responsible for the study: Tamberi Stefano. Funding: AstraZeneca. Disclosure: All authors have declared no conflicts of interest.
abstracts
663TiP
A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study
M.A. Barbera1, J. Corbelli1, G. Papiani1, E. Grassi2, G. Ugolini3, I. Montroni3, M. Di Bartolomeo4, S. Cascinu5, M. Marzola6, A. Bonetti7, G.L. Frassineti8, O. Nanni9, D. Zattoni3, F. Ghignone3, G. Taffurelli3, C. Pinto10, C. Carli Moretti11, G. Rossi12, S. Palazzi13, S. Tamberi14 1 Medical Oncology, Infermi Hospital - Faenza, Faenza, Italy, 2Department of Experimental, Diagnostic and Specialty Medicine - Dimes, AOU Policlinico S. OrsolaMalpighi, Bologna, Italy, 3Surgery Unit, Infermi Hospital - Faenza, Faenza, Italy, 4 Medical Oncology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 5Oncology, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy, 6Medical Oncology, Sant’Anna Hospital Cona-University of Ferrara, Cona, Italy, 7 Oncology, Ospedale Mater Salutis di Legnago, Legnago, Italy, 8Oncology, Istituto a Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, Italy, 9Unit di Biostatistica e Sperimentazioni Cliniche, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy, 10Clinical Canncer Center, Medical Oncology Unit, Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy, 11 Radiology Unit, Infermi Hospital - Faenza, Faenza, Italy, 12Pathology Unit, Ravenna Hospital, Ravenna, Italy, 13Radiotherapy Unit, Ravenna Hospital, Ravenna, Italy, 14 Medical Oncology, Infermi Hospital - Faenza, Faenza, Ravenna, Italy Background: The standard treatment for cT3-4 N0-1 rectal cancer is preoperative chemo-radiation therapy (CT/RT). The combination of capecitabine plus long course
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz246 | v249
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz246.140/5578202/ by guest on 07 October 2019
radiotherapy (RT) is standard therapy in locally advanced rectal cancer. Pathologic Complete remission (pCR) can be considered as surrogate end point of efficacy of treatment in terms of disease free survival (DFS). Clinical complete remission (cCR) is an important endpoint for “wait and see” strategy. In the PACIFIC trial in non-small cell lung cancer the patients were treated with durvalumab maintenance after CT/RT with advantage in progression free survival. “Abscopal effect” is proposed as mediator of systemic effects after localized RT. Preclinical data points heavily toward a strong synergy between RT and immune treatments. Recent reports already illustrate that such a systemic effect of RT is possible when enhanced by targeted immune treatments. Trial design: This is a prospective phase II, open label, single arm, multi-centre study to evaluate, in patients with operable rectal cancer, activity of an innovative sequence: standard concomitant CT/RT therapy with 825 mg/m2 twice daily capecitabine every day and 5040 cGy radiotherapy for 5 days per week for 5 weeks followed by 1500 mg Q4W durvalumab for 3 administration. After 9-10 weeks from neoadjuvant therapy will be performed re-staging with CT and MRI scan. Surgery will be performed at week 10-12 from the end of CT/RT. Primary Objective: pCR rate, defined as a TRG 3-4 according to DWORAK criteria. Secondary Objectives: Safety of treatment with durvalumab; cCR rate after durvalumab treatment before surgery and DFS. cCR will be evaluated with clinical, endoscopic and radiological assessment to look for evidence of residual disease. DFS will be evaluated during a follow up of 5 years. Exploratory Objective: Biological translational analysis of tumor biomarkers will be performed on the endoscopy biopsy done at the diagnosis and on the biopsy performed after the CT/ RT prior to treatment with durvavalumab. We have planned to enlist 60 patients in 7 centers with an enrollment period of 12 months, already underway. Clinical trial identification: 2018-004758-39. Legal entity responsible for the study: Tamberi Stefano. Funding: AstraZeneca. Disclosure: All authors have declared no conflicts of interest.