Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma

Sagun Parakh, Manreet Randhawa, Bella Nguyen, Lydia Warburton, Mohammad Akhtar Hussain, Jonathan Cebon, Michael Millward, Desmond Yip, Sayed Ali

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Abstract

Background: There is limited real-world data on the efficacy and safety of combination programmed cell death protein-1 (PD-1) inhibitor, nivolumab and the cytotoxic T-lymphocyte antigen (CTLA-4) inhibitor ipilimumab. Method: We retrospectively identified patients (pts) with metastatic melanoma treated with three-weekly nivolumab (1 mg/kg) in combination with ipilimumab (3 mg/kg) for four cycles followed by nivolumab monotherapy (3 mg/kg) fortnightly. Patient demographics and treatment parameters were collected and outcomes determined. Results: A total of 45 pts received combination treatment with a median follow up of 8.7 months (range 0.33–25.9 months). A total of 67% were male, and BRAF V600 mutations detected in 38%. At treatment commencement, 14 (31%) pts had brain metastases, 51% had an elevated LDH and 18 (40%) were treatment-naive. Almost a third (30%) required corticosteroids for symptom control or management of prior toxicities. Nineteen (42%) patients had prior anti-PD-1 therapy. The disease control rate (DCR) was 54% and objective response rate (ORR) was 29%. Of pts treated with prior immune checkpoint inhibitors, the DCR and ORR were 50% and 33%, respectively. Intracranial responses were observed in 18% (n = 2). The median progression-free survival (PFS) was 5.8 months (95% Confidence interval (CI), 2.9–14.1 months). PFS was higher in treatment naïve patients compared to those who had prior immunotherapy (6.2 months vs 4.9 months, P = 0.59). The median OS was 17.4 months (95% CI, 7.1–NR). pts requiring corticosteroids had a shorter PFS (4.9 months vs 6.8 months) and OS (7.1 months vs NR, P = 0.01).Treatment-related adverse events of any grade were experienced by 88% of pts, with 54% having grade 3–4 adverse events. Treatment discontinuation due to adverse events occurred in 44% of pts. Conclusion: In this study, responses to combination immunotherapy were lower than reported. Patients treated with prior immunotherapy had similar responses as treatment-naïve pts. The toxicity profile seen in this study is similar to those reported in clinical trials.

Original languageEnglish
JournalAsia–Pacific Journal of Clinical Oncology
DOIs
Publication statusE-pub ahead of print - 13 Nov 2018

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Melanoma
Immunotherapy
Disease-Free Survival
Therapeutics
nivolumab
ipilimumab
Programmed Cell Death 1 Receptor
Adrenal Cortex Hormones
CTLA-4 Antigen
Confidence Intervals
Demography
Clinical Trials
Neoplasm Metastasis
Safety
Mutation
Brain

Cite this

Parakh, Sagun ; Randhawa, Manreet ; Nguyen, Bella ; Warburton, Lydia ; Hussain, Mohammad Akhtar ; Cebon, Jonathan ; Millward, Michael ; Yip, Desmond ; Ali, Sayed. / Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. In: Asia–Pacific Journal of Clinical Oncology. 2018.
@article{febd3f0865c04f9bb406ed037551b96b,
title = "Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma",
abstract = "Background: There is limited real-world data on the efficacy and safety of combination programmed cell death protein-1 (PD-1) inhibitor, nivolumab and the cytotoxic T-lymphocyte antigen (CTLA-4) inhibitor ipilimumab. Method: We retrospectively identified patients (pts) with metastatic melanoma treated with three-weekly nivolumab (1 mg/kg) in combination with ipilimumab (3 mg/kg) for four cycles followed by nivolumab monotherapy (3 mg/kg) fortnightly. Patient demographics and treatment parameters were collected and outcomes determined. Results: A total of 45 pts received combination treatment with a median follow up of 8.7 months (range 0.33–25.9 months). A total of 67{\%} were male, and BRAF V600 mutations detected in 38{\%}. At treatment commencement, 14 (31{\%}) pts had brain metastases, 51{\%} had an elevated LDH and 18 (40{\%}) were treatment-naive. Almost a third (30{\%}) required corticosteroids for symptom control or management of prior toxicities. Nineteen (42{\%}) patients had prior anti-PD-1 therapy. The disease control rate (DCR) was 54{\%} and objective response rate (ORR) was 29{\%}. Of pts treated with prior immune checkpoint inhibitors, the DCR and ORR were 50{\%} and 33{\%}, respectively. Intracranial responses were observed in 18{\%} (n = 2). The median progression-free survival (PFS) was 5.8 months (95{\%} Confidence interval (CI), 2.9–14.1 months). PFS was higher in treatment na{\"i}ve patients compared to those who had prior immunotherapy (6.2 months vs 4.9 months, P = 0.59). The median OS was 17.4 months (95{\%} CI, 7.1–NR). pts requiring corticosteroids had a shorter PFS (4.9 months vs 6.8 months) and OS (7.1 months vs NR, P = 0.01).Treatment-related adverse events of any grade were experienced by 88{\%} of pts, with 54{\%} having grade 3–4 adverse events. Treatment discontinuation due to adverse events occurred in 44{\%} of pts. Conclusion: In this study, responses to combination immunotherapy were lower than reported. Patients treated with prior immunotherapy had similar responses as treatment-na{\"i}ve pts. The toxicity profile seen in this study is similar to those reported in clinical trials.",
keywords = "ipilimumab, metastatic melanoma, nivolumab",
author = "Sagun Parakh and Manreet Randhawa and Bella Nguyen and Lydia Warburton and Hussain, {Mohammad Akhtar} and Jonathan Cebon and Michael Millward and Desmond Yip and Sayed Ali",
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Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. / Parakh, Sagun; Randhawa, Manreet; Nguyen, Bella; Warburton, Lydia; Hussain, Mohammad Akhtar; Cebon, Jonathan; Millward, Michael; Yip, Desmond; Ali, Sayed.

In: Asia–Pacific Journal of Clinical Oncology, 13.11.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma

AU - Parakh, Sagun

AU - Randhawa, Manreet

AU - Nguyen, Bella

AU - Warburton, Lydia

AU - Hussain, Mohammad Akhtar

AU - Cebon, Jonathan

AU - Millward, Michael

AU - Yip, Desmond

AU - Ali, Sayed

PY - 2018/11/13

Y1 - 2018/11/13

N2 - Background: There is limited real-world data on the efficacy and safety of combination programmed cell death protein-1 (PD-1) inhibitor, nivolumab and the cytotoxic T-lymphocyte antigen (CTLA-4) inhibitor ipilimumab. Method: We retrospectively identified patients (pts) with metastatic melanoma treated with three-weekly nivolumab (1 mg/kg) in combination with ipilimumab (3 mg/kg) for four cycles followed by nivolumab monotherapy (3 mg/kg) fortnightly. Patient demographics and treatment parameters were collected and outcomes determined. Results: A total of 45 pts received combination treatment with a median follow up of 8.7 months (range 0.33–25.9 months). A total of 67% were male, and BRAF V600 mutations detected in 38%. At treatment commencement, 14 (31%) pts had brain metastases, 51% had an elevated LDH and 18 (40%) were treatment-naive. Almost a third (30%) required corticosteroids for symptom control or management of prior toxicities. Nineteen (42%) patients had prior anti-PD-1 therapy. The disease control rate (DCR) was 54% and objective response rate (ORR) was 29%. Of pts treated with prior immune checkpoint inhibitors, the DCR and ORR were 50% and 33%, respectively. Intracranial responses were observed in 18% (n = 2). The median progression-free survival (PFS) was 5.8 months (95% Confidence interval (CI), 2.9–14.1 months). PFS was higher in treatment naïve patients compared to those who had prior immunotherapy (6.2 months vs 4.9 months, P = 0.59). The median OS was 17.4 months (95% CI, 7.1–NR). pts requiring corticosteroids had a shorter PFS (4.9 months vs 6.8 months) and OS (7.1 months vs NR, P = 0.01).Treatment-related adverse events of any grade were experienced by 88% of pts, with 54% having grade 3–4 adverse events. Treatment discontinuation due to adverse events occurred in 44% of pts. Conclusion: In this study, responses to combination immunotherapy were lower than reported. Patients treated with prior immunotherapy had similar responses as treatment-naïve pts. The toxicity profile seen in this study is similar to those reported in clinical trials.

AB - Background: There is limited real-world data on the efficacy and safety of combination programmed cell death protein-1 (PD-1) inhibitor, nivolumab and the cytotoxic T-lymphocyte antigen (CTLA-4) inhibitor ipilimumab. Method: We retrospectively identified patients (pts) with metastatic melanoma treated with three-weekly nivolumab (1 mg/kg) in combination with ipilimumab (3 mg/kg) for four cycles followed by nivolumab monotherapy (3 mg/kg) fortnightly. Patient demographics and treatment parameters were collected and outcomes determined. Results: A total of 45 pts received combination treatment with a median follow up of 8.7 months (range 0.33–25.9 months). A total of 67% were male, and BRAF V600 mutations detected in 38%. At treatment commencement, 14 (31%) pts had brain metastases, 51% had an elevated LDH and 18 (40%) were treatment-naive. Almost a third (30%) required corticosteroids for symptom control or management of prior toxicities. Nineteen (42%) patients had prior anti-PD-1 therapy. The disease control rate (DCR) was 54% and objective response rate (ORR) was 29%. Of pts treated with prior immune checkpoint inhibitors, the DCR and ORR were 50% and 33%, respectively. Intracranial responses were observed in 18% (n = 2). The median progression-free survival (PFS) was 5.8 months (95% Confidence interval (CI), 2.9–14.1 months). PFS was higher in treatment naïve patients compared to those who had prior immunotherapy (6.2 months vs 4.9 months, P = 0.59). The median OS was 17.4 months (95% CI, 7.1–NR). pts requiring corticosteroids had a shorter PFS (4.9 months vs 6.8 months) and OS (7.1 months vs NR, P = 0.01).Treatment-related adverse events of any grade were experienced by 88% of pts, with 54% having grade 3–4 adverse events. Treatment discontinuation due to adverse events occurred in 44% of pts. Conclusion: In this study, responses to combination immunotherapy were lower than reported. Patients treated with prior immunotherapy had similar responses as treatment-naïve pts. The toxicity profile seen in this study is similar to those reported in clinical trials.

KW - ipilimumab

KW - metastatic melanoma

KW - nivolumab

UR - http://www.scopus.com/inward/record.url?scp=85056403284&partnerID=8YFLogxK

U2 - 10.1111/ajco.13100

DO - 10.1111/ajco.13100

M3 - Article

JO - Asia–Pacific Journal of Clinical Oncology

JF - Asia–Pacific Journal of Clinical Oncology

SN - 1743-7555

ER -