Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: The non-interventional study coveNIS

Katharina C. Kähler; Dirk Debus; Gaston Schley; Daniela Göppner; Jessica C. Hassel; Friedegund Meier; Patrick Terheyden; Rudolf Stadler; Thomas Tüting; Martin Kaatz; Norman Philipp Hoff; Ehsan Masoudi; Agnieszka Zdanowicz-Specht; Minh Tam Nguyen; Peter Mohr

doi:10.1097/CMR.0000000000000908

Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: The non-interventional study coveNIS

Katharina C. Kähler, Dirk Debus, Gaston Schley, Daniela Göppner, Jessica C. Hassel, Friedegund Meier, Patrick Terheyden, Rudolf Stadler, Thomas Tüting, Martin Kaatz, Norman Philipp Hoff, Ehsan Masoudi, Agnieszka Zdanowicz-Specht, Minh Tam Nguyen, Peter Mohr^*

^*Corresponding author for this work

Abstract

Cobimetinib/vemurafenib combination therapy is approved for treatment of adults with unresectable or metastatic BRAF V600 mutated malignant melanoma (mM). The non-interventional post-authorisation safety study coveNIS collected real-world data on cobimetinib/vemurafenib treatment focussing on overall survival (OS), safety and utilization. MM patients with brain metastases are usually excluded from clinical studies. coveNIS observed 2 cohorts: mM patients without (Cohort A) and with cerebral metastases (Cohort B), aiming to close the data gap for the latter population. A direct comparison of the 2 cohorts was not intended. The primary effectiveness objective was OS; the safety objective was the incidence of all and of serious adverse events (AEs). Secondary objectives included progression-free survival (PFS), time to development of cerebral metastasis (Cohort A) and time to central nervous system relapse (Cohort B). All statistical analyses were descriptive. Between 2017 and 2021, 95 patients were included (Cohort A: 54, Cohort B: 41 patients) at 32 sites in Germany. Median OS was 21.6 months in Cohort A, 7.4 months in Cohort B. Median PFS was 6.9 months in Cohort A, 5.2 months in Cohort B. The proportion of patients experiencing any AEs was 83.3% (Cohort A) and 87.8% (Cohort B). The two most common AEs in Cohort A were 'diarrhoea' (37%), 'vomiting' (20.4%) and 'pyrexia' (20.4%); in Cohort B 'diarrhoea' (36.6%) and 'fatigue' (22%). In conclusion, the OS rates in Cohort A and Cohort B of coveNIS are in line with the OS data from other trials with BRAF/MEK inhibitors for mM. No new safety signals were observed.

Original language	English
Journal	Melanoma Research
Volume	34
Issue number	1
Pages (from-to)	44-53
Number of pages	10
ISSN	0960-8931
DOIs	https://doi.org/10.1097/CMR.0000000000000908
Publication status	Published - 01.2024

Funding

This study was funded by Roche Pharma AG, Grenzach-Wyhlen, Germany. Roche was involved in the design and conduct of the study; collection, management, analysis and interpretation of data; and preparation, review and approval of the article. The authors would like to thank the patients, physicians and site staff who participated in this study. Anna Schuler managed the clinical study report process. Nadine Schmidt and Susanne Koch were involved in the safety data management. Pauline Gerard-Duhard reviewed the clinical study report. Editorial support in drafting the article was provided by Hanna Neymeyer and Michael Stauber of AMS Advanced Medical Services GmbH, with funding from Roche Pharma AG; Grenzach-Wyhlen, Germany, prior to review, revision and the decision to publish by the authors.

Research Areas and Centers

Research Area: Luebeck Integrated Oncology Network (LION)
Centers: University Cancer Center Schleswig-Holstein (UCCSH)

DFG Research Classification Scheme

2.22-19 Dermatology
2.22-14 Hematology, Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/CMR.0000000000000908

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Kähler, K. C., Debus, D., Schley, G., Göppner, D., Hassel, J. C., Meier, F., Terheyden, P., Stadler, R., Tüting, T., Kaatz, M., Hoff, N. P., Masoudi, E., Zdanowicz-Specht, A., Nguyen, M. T., & Mohr, P. (2024). Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: The non-interventional study coveNIS. Melanoma Research, 34(1), 44-53. https://doi.org/10.1097/CMR.0000000000000908

@article{2f3a72acab38488aa5fe65504fa33d94,

title = "Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: The non-interventional study coveNIS",

abstract = "Cobimetinib/vemurafenib combination therapy is approved for treatment of adults with unresectable or metastatic BRAF V600 mutated malignant melanoma (mM). The non-interventional post-authorisation safety study coveNIS collected real-world data on cobimetinib/vemurafenib treatment focussing on overall survival (OS), safety and utilization. MM patients with brain metastases are usually excluded from clinical studies. coveNIS observed 2 cohorts: mM patients without (Cohort A) and with cerebral metastases (Cohort B), aiming to close the data gap for the latter population. A direct comparison of the 2 cohorts was not intended. The primary effectiveness objective was OS; the safety objective was the incidence of all and of serious adverse events (AEs). Secondary objectives included progression-free survival (PFS), time to development of cerebral metastasis (Cohort A) and time to central nervous system relapse (Cohort B). All statistical analyses were descriptive. Between 2017 and 2021, 95 patients were included (Cohort A: 54, Cohort B: 41 patients) at 32 sites in Germany. Median OS was 21.6 months in Cohort A, 7.4 months in Cohort B. Median PFS was 6.9 months in Cohort A, 5.2 months in Cohort B. The proportion of patients experiencing any AEs was 83.3\% (Cohort A) and 87.8\% (Cohort B). The two most common AEs in Cohort A were 'diarrhoea' (37\%), 'vomiting' (20.4\%) and 'pyrexia' (20.4\%); in Cohort B 'diarrhoea' (36.6\%) and 'fatigue' (22\%). In conclusion, the OS rates in Cohort A and Cohort B of coveNIS are in line with the OS data from other trials with BRAF/MEK inhibitors for mM. No new safety signals were observed.",

author = "K{\"a}hler, \{Katharina C.\} and Dirk Debus and Gaston Schley and Daniela G{\"o}ppner and Hassel, \{Jessica C.\} and Friedegund Meier and Patrick Terheyden and Rudolf Stadler and Thomas T{\"u}ting and Martin Kaatz and Hoff, \{Norman Philipp\} and Ehsan Masoudi and Agnieszka Zdanowicz-Specht and Nguyen, \{Minh Tam\} and Peter Mohr",

year = "2024",

month = jan,

doi = "10.1097/CMR.0000000000000908",

language = "English",

volume = "34",

pages = "44--53",

journal = "Melanoma Research",

issn = "0960-8931",

publisher = "Lippincott Williams and Wilkins",

number = "1",

}

Kähler, KC, Debus, D, Schley, G, Göppner, D, Hassel, JC, Meier, F, Terheyden, P, Stadler, R, Tüting, T, Kaatz, M, Hoff, NP, Masoudi, E, Zdanowicz-Specht, A, Nguyen, MT & Mohr, P 2024, 'Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: The non-interventional study coveNIS', Melanoma Research, vol. 34, no. 1, pp. 44-53. https://doi.org/10.1097/CMR.0000000000000908

Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: The non-interventional study coveNIS. / Kähler, Katharina C.; Debus, Dirk; Schley, Gaston et al.
In: Melanoma Research, Vol. 34, No. 1, 01.2024, p. 44-53.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany

T2 - The non-interventional study coveNIS

AU - Kähler, Katharina C.

AU - Debus, Dirk

AU - Schley, Gaston

AU - Göppner, Daniela

AU - Hassel, Jessica C.

AU - Meier, Friedegund

AU - Terheyden, Patrick

AU - Stadler, Rudolf

AU - Tüting, Thomas

AU - Kaatz, Martin

AU - Hoff, Norman Philipp

AU - Masoudi, Ehsan

AU - Zdanowicz-Specht, Agnieszka

AU - Nguyen, Minh Tam

AU - Mohr, Peter

PY - 2024/1

Y1 - 2024/1

N2 - Cobimetinib/vemurafenib combination therapy is approved for treatment of adults with unresectable or metastatic BRAF V600 mutated malignant melanoma (mM). The non-interventional post-authorisation safety study coveNIS collected real-world data on cobimetinib/vemurafenib treatment focussing on overall survival (OS), safety and utilization. MM patients with brain metastases are usually excluded from clinical studies. coveNIS observed 2 cohorts: mM patients without (Cohort A) and with cerebral metastases (Cohort B), aiming to close the data gap for the latter population. A direct comparison of the 2 cohorts was not intended. The primary effectiveness objective was OS; the safety objective was the incidence of all and of serious adverse events (AEs). Secondary objectives included progression-free survival (PFS), time to development of cerebral metastasis (Cohort A) and time to central nervous system relapse (Cohort B). All statistical analyses were descriptive. Between 2017 and 2021, 95 patients were included (Cohort A: 54, Cohort B: 41 patients) at 32 sites in Germany. Median OS was 21.6 months in Cohort A, 7.4 months in Cohort B. Median PFS was 6.9 months in Cohort A, 5.2 months in Cohort B. The proportion of patients experiencing any AEs was 83.3% (Cohort A) and 87.8% (Cohort B). The two most common AEs in Cohort A were 'diarrhoea' (37%), 'vomiting' (20.4%) and 'pyrexia' (20.4%); in Cohort B 'diarrhoea' (36.6%) and 'fatigue' (22%). In conclusion, the OS rates in Cohort A and Cohort B of coveNIS are in line with the OS data from other trials with BRAF/MEK inhibitors for mM. No new safety signals were observed.

AB - Cobimetinib/vemurafenib combination therapy is approved for treatment of adults with unresectable or metastatic BRAF V600 mutated malignant melanoma (mM). The non-interventional post-authorisation safety study coveNIS collected real-world data on cobimetinib/vemurafenib treatment focussing on overall survival (OS), safety and utilization. MM patients with brain metastases are usually excluded from clinical studies. coveNIS observed 2 cohorts: mM patients without (Cohort A) and with cerebral metastases (Cohort B), aiming to close the data gap for the latter population. A direct comparison of the 2 cohorts was not intended. The primary effectiveness objective was OS; the safety objective was the incidence of all and of serious adverse events (AEs). Secondary objectives included progression-free survival (PFS), time to development of cerebral metastasis (Cohort A) and time to central nervous system relapse (Cohort B). All statistical analyses were descriptive. Between 2017 and 2021, 95 patients were included (Cohort A: 54, Cohort B: 41 patients) at 32 sites in Germany. Median OS was 21.6 months in Cohort A, 7.4 months in Cohort B. Median PFS was 6.9 months in Cohort A, 5.2 months in Cohort B. The proportion of patients experiencing any AEs was 83.3% (Cohort A) and 87.8% (Cohort B). The two most common AEs in Cohort A were 'diarrhoea' (37%), 'vomiting' (20.4%) and 'pyrexia' (20.4%); in Cohort B 'diarrhoea' (36.6%) and 'fatigue' (22%). In conclusion, the OS rates in Cohort A and Cohort B of coveNIS are in line with the OS data from other trials with BRAF/MEK inhibitors for mM. No new safety signals were observed.

UR - https://www.scopus.com/pages/publications/85181016901

UR - https://www.mendeley.com/catalogue/65f2bda3-8075-31a1-acfb-dbca49b76239/

U2 - 10.1097/CMR.0000000000000908

DO - 10.1097/CMR.0000000000000908

M3 - Journal articles

C2 - 37962220

AN - SCOPUS:85181016901

SN - 0960-8931

VL - 34

SP - 44

EP - 53

JO - Melanoma Research

JF - Melanoma Research

IS - 1

ER -

Kähler KC, Debus D, Schley G, Göppner D, Hassel JC, Meier F et al. Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: The non-interventional study coveNIS. Melanoma Research. 2024 Jan;34(1):44-53. doi: 10.1097/CMR.0000000000000908

Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: The non-interventional study coveNIS

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

Access to Document

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