Side Effects of cobimetinib: A Synthesis of Findings from 21 Studies

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Original Abstract of the Article

Major Research Findings

Cobimetinib, when combined with vemurafenib, a BRAF inhibitor, has shown to be effective in treating metastatic melanoma with BRAF V600 mutations. 20 21 This combination improves progression-free survival, reduces skin side effects of vemurafenib, and potentially improves renal side effects of vemurafenib. 18

Reasons for Side Effects

Cobimetinib is a MEK inhibitor that targets the MAPK pathway, which is crucial for cell growth and differentiation. By inhibiting this pathway, cobimetinib effectively slows down melanoma cell growth, but it can also affect normal cells, potentially leading to side effects. 20 2

Common Side Effects

Skin

Cobimetinib can cause skin side effects, but the combination with vemurafenib is known to reduce these effects. 18 16 14 12

Heart

Cobimetinib can cause heart side effects, and the combination with vemurafenib may worsen them. 13 16

Eyes

Cobimetinib can cause eye side effects. 6 5 9 16

Digestive System

Cobimetinib can cause digestive system side effects. 16

Kidneys

Cobimetinib can cause kidney side effects, but the combination with vemurafenib might reduce these effects. 18

Blood

Cobimetinib can cause blood side effects. 8 16

Muscles

Cobimetinib can cause muscle side effects. 15 16

Nervous System

Cobimetinib can cause nervous system side effects. 16

Countermeasures for Side Effects

Skin Side Effects

If you experience skin side effects, consult your doctor. 16 12 14 18

Heart Side Effects

If you experience heart side effects, consult your doctor immediately. 16 13 You may need to stop taking cobimetinib. 13

Eye Side Effects

If you experience eye side effects, consult an ophthalmologist immediately. 6 5 9

Digestive System Side Effects

If you experience digestive system side effects, consult your doctor. 16

Kidney Side Effects

If you experience kidney side effects, consult your doctor. 18

Blood Side Effects

If you experience blood side effects, consult your doctor. 8 16

Muscle Side Effects

If you experience muscle side effects, consult your doctor. 15 16

Nervous System Side Effects

If you experience nervous system side effects, consult your doctor. 16

Comparison of Studies

Common Points

Many studies have shown that cobimetinib, in combination with BRAF inhibitors, is effective in treating metastatic melanoma. 21 20 18 16 2

Differences

Different results have been reported regarding the side effects of cobimetinib. 18 13 8 6 5 9 15 12

Points to Note Regarding Application to Real Life

Cobimetinib is an effective treatment for metastatic melanoma with BRAF V600 mutations, but it also carries the risk of side effects. 21 20 When considering the use of cobimetinib, it is important to consult with your doctor and understand the benefits and risks. 16

Limitations of Current Research

Research on the side effects of cobimetinib is still insufficient. 20 11 Further research is needed. 3

Future Research Directions

Research is needed to clarify the mechanism of development of cobimetinib side effects and to develop new treatments that can reduce side effects. 14 Identifying predictors of cobimetinib side effects could potentially lead to safer treatments. 2

Conclusion

Cobimetinib, in combination with BRAF inhibitors, has been shown to be effective in treating metastatic melanoma. 21 20 However, it also carries the risk of side effects, so it is important to consult with your doctor and understand the benefits and risks. 16

Literature analysis of 21 papers
Positive Content
20
Neutral Content
0
Negative Content
1
Article Type
1
0
0
8
18
1.

Potential drug-drug interactions with mitogen-activated protein kinase (MEK) inhibitors used to treat melanoma.

Author: MaraniA, GioacchiniH, PaolinelliM, OffidaniA, CampanatiA

Targeted therapy for melanoma
Drug interactions
Increased toxicity

This review examines drug-drug interactions associated with MEK inhibitors, which are used for the treatment of BRAF-mutated advanced melanoma. The review highlights the potential benefits and increased toxicity of these interactions, emphasizing the need for careful medication management in this patient population.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

4.

Efficacy and toxicity of vemurafenib and cobimetinib in relation to plasma concentrations, after administration via feeding tube in patients with BRAF-mutated thyroid cancer: a case series and review of literature.

Author: van Berge HenegouwenJ M, van der WijngaartH, ZeverijnL J, HoesL R, MeertensM, HuitemaA D R, DevrieseL A, LabotsM, VerheulH M W, VoestE E, GelderblomH

Improve survival

This study describes the off-label treatment of BRAF V600-mutated thyroid carcinoma with a combination of vemurafenib and cobimetinib, approved for melanoma.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Mitogen-activated protein kinase inhibitor-associated retinopathy (MEKAR). A clinical case.

Author: Buenasmañanas-MaesoM, Gutiérrez-MonteroÓ, Reche-SainzJ A, Badillo ArconesE, Monja-AlarcónN, Toledano-FernándezN

Improved cancer prognosis
Neurosensory detachments

This case report describes a 55-year-old woman who developed bilateral neurosensory detachments and blurred vision while on a MEK inhibitor for metastatic melanoma. This retinopathy, known as MEKAR, resolved upon discontinuation of the treatment.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

6.

[Ocular toxicity of targeted therapies with MEK inhibitors and BRAF inhibitors in the treatment of metastatic cutaneous melanoma].

Author: FauviauxE, PromelleV, BoucennaV, JanyB, ErreraM H, DelbarreM, BoucennaW

Improved survival rate
Ocular toxicity

This study assessed the incidence, clinical features, and management of ocular complications caused by MEK inhibitors and BRAF inhibitors used for treating metastatic melanoma. While these targeted therapies improve survival rates, they can lead to ocular toxicity. Understanding the potential risks and appropriate management strategies is crucial.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.

Language : French

7.

First-line treatment of NRAS-mutated metastatic melanoma with a MEK inhibitor.

Author: BickelAngelika, DiemStefan, FlatzLukas, StinnBjörn, SianoMarco

Melanoma treatment
Partial remission
Cerebral hemorrhage

This case report describes an 84-year-old patient with widespread metastatic melanoma harboring an NRAS mutation who achieved good partial remission with cobimetinib treatment.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

8.

Hemophagocytic lymphohistiocytosis of a melanoma patient under BRAF/MEK-inhibitor therapy following anti-PD1 inhibitor treatment: a case report and review to the literature.

Author: DuddaMilena, MannCaroline, HeinzJaqueline, SchmidgenIsabel, WeidFlorian, KühnM, SalogaJoachim, GrabbeStephan, LoquaiCarmen

HLH treatment

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening condition. This case report highlights the importance of early diagnosis and treatment with steroids.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

A novel side effect of mitogen-activated protein kinase inhibitor cobimetinib: Acute corneal decompensation.

Author: AsfurogluMahmut, AsfuroğluYonca

Corneal decompensation

This case report describes a patient with BRAF-mutated metastatic melanoma who experienced corneal decompensation as a side effect of cobimetinib and vemurafenib treatment.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

Panniculitis Under Successful Targeted Inhibition of the MAPK/ERK Signaling Pathway in a Patient With BRAF V600E-mutated Spindle Cell Oncocytoma of the Pituitary Gland.

Author: SollfrankLukas, LettmaierSebastian, ErdmannMichael, UsluUgur

SCO treatment

Spindle cell oncocytoma (SCO) of the pituitary gland is a rare tumor. Mutational analysis and targeted therapy may be beneficial in treating SCO, as surgical excision and radiation therapy often result in local recurrences.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

11.

Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management.

Author: HeinzerlingLucie, EigentlerThomas K, FluckMichael, HasselJessica C, Heller-SchenckDaniela, LeipeJan, PauschingerMatthias, VogelArndt, ZimmerLisa, GutzmerRalf

BRAFi+MEKi therapy
Well-tolerated
Anaemia
Cardiac events
Cutaneous events
Facial paresis
Fever
Gastrointestinal events
Increased liver function tests
Musculoskeletal events
Neutropenia
Ocular events
Photosensitivity
QTc prolongation
Skin rash

Combining BRAF and MEK inhibitors has become a standard treatment for melanoma patients with BRAF mutations. This review examines the safety profiles of three BRAF/MEK inhibitor combinations, focusing on common side effects like skin rashes, gastrointestinal problems, and heart-related issues.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

12.

Cobimetinib- and vemurafenib-induced granulomatous dermatitis and erythema induratum: A case report.

Author: IafollaMarco Aj, RamsayJennifer, WismerJudy, McWhirterElaine

Attenuated toxicities
Increased survival
Erythema induratum
Granulomatous dermatitis

BRAF and MEK inhibitors together can improve survival for metastatic melanoma patients, but these drugs may cause skin problems like granulomatous dermatitis and erythema induratum.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

13.

Cardiac toxicity of combined vemurafenib and cobimetinib administration
.

Author: FiocchiRoberto, GoriMauro, TaddeiFilippo, TrevisaniLaura, GalloMariapina, EleftheriouGeorgios

Cardiac recovery
Cardiac effects
Ventricular fibrillation

This case report describes a patient who experienced potentially fatal cardiac side effects, including prolonged QTc interval and reduced left ventricular ejection fraction, after treatment with vemurafenib and cobimetinib for metastatic melanoma. The report highlights the time course of recovery after these side effects, with complete normalization of cardiac function occurring within six months.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

14.

BRAF inhibitors stimulate inflammasome activation and interleukin 1 beta production in dendritic cells.

Author: HajekEva, KrebsFranziska, BentRebekka, HaasKatharina, BastAntje, SteinmetzIvo, TuettenbergAndrea, GrabbeStephan, BrosMatthias

Melanoma treatment
Tumor immune response
Inflammasome activation
Pro-inflammatory side effects

BRAF<sup>V600E</sup> inhibitors, Vemurafenib (VEM) and Dabrafenib (DAB), were found to modulate dendritic cell (DC) function and induce IL-1β release. DAB, to a greater extent than VEM, activated the NLRC4/Caspase-1 inflammasome in mouse and human DCs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

15.

Success of rechallenging dabrafenib and trametinib combination therapy after trametinib-induced rhabdomyolysis: a case report.

Author: MutoYusuke, NgWilliam, NamikawaKenjiro, TakahashiAkira, TsutsumidaArata, NishidaMakiko, YamazakiNaoya

Melanoma treatment
Rhabdomyolysis

A combination therapy of dabrafenib and trametinib was effective for BRAF-mutant advanced melanomas, but a rare adverse event of rhabdomyolysis was reported.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

16.

Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma.

Author: DaudAdil, TsaiKaty

Improved survival
Prolonged survival
Drug-related adverse events
Toxicity

This review discusses the toxicity profiles of BRAF and MEK inhibitors used to treat advanced-stage BRAF V600-mutant melanoma. It provides practical guidance for managing key drug-related adverse events.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

17.

Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study.

Author: DrénoB, RibasA, LarkinJ, AsciertoP A, HauschildA, ThomasL, GrobJ-J, KoralekD O, RooneyI, HsuJ J, McKennaE F, McArthurG A

Improved survival
Progression-free survival

This report details the incidence, course, and management of key adverse events (AEs) in the coBRIM phase III trial, which investigated the combination of cobimetinib and vemurafenib for advanced BRAF-mutated melanoma.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

21.

BRAF and MEK inhibition in melanoma.

Author: DossettLesly A, KudchadkarRagini R, ZagerJonathan S

Melanoma response
Survival improvement

This review discusses the use of BRAF and MEK inhibitors in combination therapy for BRAF-mutant metastatic melanoma, highlighting its potential to improve efficacy and reduce side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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