Second-line therapy with nivolumab plus ipilimumab for older patients with oesophageal squamous cell cancer (RAMONA): a multicentre, open-label phase 2 trial

Matthias P Ebert, ProfMD; Nadja M Meindl-Beinker, PhD; Tobias Gutting, MD; Martin Maenz, PhD; Johannes Betge, MD; Nadine Schulte, MD; Tianzuo Zhan, MD; Philip Weidner, MD; Elke Burgermeister, PhD; Ralf Hofheinz, ProfMD; Arndt Vogel, ProfMD; Stefan Angermeier, MD; Claus Bolling, MD; Maike de Wit, ProfMD; Ralf Jakobs, ProfMD; Meinolf Karthaus, ProfMD; Gertraud Stocker, MD; Peter Thuss-Patience, MD; Tobias Leidig, PhD; Timo Gaiser, ProfMD; Jakob N Kather, ProfMD; Nicolai Haertel, MD

The Lancet. Healthy Longevity (Jun 2022)

Second-line therapy with nivolumab plus ipilimumab for older patients with oesophageal squamous cell cancer (RAMONA): a multicentre, open-label phase 2 trial

Matthias P Ebert, ProfMD,
Nadja M Meindl-Beinker, PhD,
Tobias Gutting, MD,
Martin Maenz, PhD,
Johannes Betge, MD,
Nadine Schulte, MD,
Tianzuo Zhan, MD,
Philip Weidner, MD,
Elke Burgermeister, PhD,
Ralf Hofheinz, ProfMD,
Arndt Vogel, ProfMD,
Stefan Angermeier, MD,
Claus Bolling, MD,
Maike de Wit, ProfMD,
Ralf Jakobs, ProfMD,
Meinolf Karthaus, ProfMD,
Gertraud Stocker, MD,
Peter Thuss-Patience, MD,
Tobias Leidig, PhD,
Timo Gaiser, ProfMD,
Jakob N Kather, ProfMD,
Nicolai Haertel, MD

Affiliations

Matthias P Ebert, ProfMD: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Institute for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany; Correspondence to: Prof Matthias P Ebert, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, D-68167 Mannheim, Germany
Nadja M Meindl-Beinker, PhD: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Tobias Gutting, MD: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Martin Maenz, PhD: AIO Studien, Berlin, Germany
Johannes Betge, MD: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany; Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models, German Cancer Research Center, Heidelberg, Germany
Nadine Schulte, MD: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Tianzuo Zhan, MD: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Philip Weidner, MD: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Elke Burgermeister, PhD: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Ralf Hofheinz, ProfMD: Interdisciplinary Tumor Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Arndt Vogel, ProfMD: Department of Gastroenterology, Hepatology und Endocrinology, Hannover Medical School, Hannover, Germany
Stefan Angermeier, MD: Department of Internal Medicine I, Klinikum Ludwigsburg, Ludwigsburg, Germany
Claus Bolling, MD: Department of Internal Medicine, Agaplesion Markus Krankenhaus Frankfurt, Diakonie Kliniken, Frankfurt, Germany
Maike de Wit, ProfMD: Department of Internal Medicine, Hematology, Oncology and Palliative Medicine, Vivantes Klinikum Neukölln, Berlin, Germany
Ralf Jakobs, ProfMD: Department of Medicine C, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany
Meinolf Karthaus, ProfMD: Department of Hematology, Oncology and Palliative Care, Klinikum Neuperlach, Munich, Germany
Gertraud Stocker, MD: University Cancer Center, University Medicine Leipzig, Leipzig, Germany
Peter Thuss-Patience, MD: Department of Hematology, Medical Oncology and Tumor Immunology, Charité Universitätsmedizin, Berlin, Germany
Tobias Leidig, PhD: CROLLL, Nuremberg, Germany
Timo Gaiser, ProfMD: Institute of Pathology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Jakob N Kather, ProfMD: Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Nicolai Haertel, MD: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

Journal volume & issue: Vol. 3, no. 6
pp. e417 – e427

Abstract

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Summary: Background: The overall survival of patients with advanced and refractory oesophageal squamous cell carcinoma, mostly aged 65 years and older, is poor. Treatment with PD-1 antibodies showed improved progression-free survival and overall survival. We assessed the safety and efficacy of combined nivolumab and ipilimumab therapy in this population. Methods: This multicentre, open-label, phase 2 trial done in 32 sites in Germany included patients aged 65 years and older with oesophageal squamous cell carcinoma and disease progression or recurrence following first-line therapy. Patients were treated with nivolumab (240 mg fixed dose once every 2 weeks, intravenously) in the safety run-in phase and continued with nivolumab and ipilimumab (nivolumab 240 mg fixed dose once every 2 weeks and ipilimumab 1 mg/kg once every 6 weeks, intravenously). The primary endpoint was overall survival, which was compared with a historical cohort receiving standard chemotherapy in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03416244. Findings: Between March 2, 2018, and Aug 20, 2020, we screened 75 patients with advanced oesophageal squamous cell carcinoma. We enrolled 66 patients (50 [76%] men and 16 [24%] women; median age 70·5 years [IQR 67·0–76·0]), 44 (67%) of whom received combined nivolumab and ipilimumab therapy and 22 (33%) received nivolumab alone. Median overall survival time at the prespecified data cutoff was 7·2 months (95% CI 5·7–12·4) and significantly higher than in a historical cohort receiving standard chemotherapy (p=0·0063). The most common treatment-related adverse events were fatigue (12 [29%] of 42), nausea (11 [26%]), and diarrhoea (ten [24%]). Grade 3–5 treatment-related adverse events occurred in 13 (20%) of 66 patients. Treatment-related death occurred in one patient with bronchiolitis obliterans while on nivolumab and ipilimumab treatment. Interpretation: Patients aged at least 65 years, with advanced oesophageal squamous cell carcinoma might benefit from combined nivolumab and ipilimumab therapy in second-line treatment. Funding: Bristol Myers Squibb.

Published in The Lancet. Healthy Longevity

ISSN: 2666-7568 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Special situations and conditions: Geriatrics
Website: https://www.thelancet.com/journals/lanhl/home

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