Myositis – A common but underreported adverse effect of osimertinib: Case series and review of the literature

Parafianowicz, Pawel; Krishan, Rohee; Beutler, Bryce D.; Islam, Raheel; Singh, Tejvir

doi:10.1016/j.ctarc.2020.100254

Cited by 9 publications

(17 citation statements)

References 16 publications

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“…It is commonly considered that the diagnosis of RM is established when patients present with myalgia or muscle weakness, combined with a serum CK level ≥1,000 U/L or ≥ five times the upper limit (4,5). Serum CK levels are slightly elevated in myositis and notably in RM; lower serum CK levels may more appropriately be defined as osimertinib-associated myositis, which is accompanied by myalgia or muscle weakness, and usually without myoglobinemia or myoglobinuria (3). Neither myositis nor RM has been officially reported as a side effect of osimertinib in major studies; nevertheless, manifestations of muscle damage including fatigue, weakness, and increased liver enzymes were observed in the AURA2, AURA3, and FLAURA studies (3,(6)(7)(8).…”

Section: Discussionmentioning

confidence: 99%

“…Serum CK levels are slightly elevated in myositis and notably in RM; lower serum CK levels may more appropriately be defined as osimertinib-associated myositis, which is accompanied by myalgia or muscle weakness, and usually without myoglobinemia or myoglobinuria (3). Neither myositis nor RM has been officially reported as a side effect of osimertinib in major studies; nevertheless, manifestations of muscle damage including fatigue, weakness, and increased liver enzymes were observed in the AURA2, AURA3, and FLAURA studies (3,(6)(7)(8). In this case, after receiving the treatment of osimertinib plus bevacizumab, the patient demonstrated a satisfying treatment response in the beginning.…”

Section: Discussionmentioning

confidence: 99%

“…Activating mutations in epidermal growth factor receptor (EGFR) are observed in 15-50% of non-small cell lung cancer (NSCLC) patients (2). Osimertinib has been approved by the U.S. Food & Drug Administation (FDA) for the first-line treatment of patients with metastatic NSCLC and EGFR mutations and those with T790Mpositive NSCLC who progressed on prior EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment (3). Osimertinib was reported to have a better tolerability in patients with locally advanced and metastatic EGFR-positive NSCLC than the first and second generation EGFR-TKIs, the most common osimertinib-associated adverse events were rash, diarrhea, nausea, dry skin, paronychia and stomatitis (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…Osimertinib was reported to have a better tolerability in patients with locally advanced and metastatic EGFR-positive NSCLC than the first and second generation EGFR-TKIs, the most common osimertinib-associated adverse events were rash, diarrhea, nausea, dry skin, paronychia and stomatitis (4)(5)(6). Previous clinical study has reported that the incidence of myositis associated with osimertinib is less than 1%, except for one retrospective study, which showed that symptomatic myositis or asymptomatic serum creatine kinase (CK) elevation occurred in over 10% (4/38) of patients treated with osimertinib (3).…”

Section: Introductionmentioning

confidence: 99%

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Rhabdomyolysis in a patient with advanced lung cancer treated with osimertinib: a case report

Li¹,

Liu²,

Zhao³

et al. 2023

Transl Lung Cancer Res

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Background: As a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib is the standard treatment for patients with EGFR mutations. Diarrhea and rash are the most common side effects, and some rare adverse reactions have started appearing owing to their increased clinical application. Osimertinib-associated myositis was reported to be more common compared with previous studies; however, osimertinib-associated rhabdomyolysis (RM) has not yet been reported. This is the first report of osimertinib-associated RM during the treatment of a lung adenocarcinoma patient with EGFR exon 19 deletion and T790M mutation. Compared to myositis, RM could lead to much more serious consequences, such as acute renal failure (ARF), disseminated intravascular coagulation (DIC) and electrolyte disturbances. Our case exemplifies the symptoms, diagnosis and treatment of osimertinib-associated RM, meanwhile, the potential mechanisms and related therapeutic choices have been fully discussed.Case Description: Herein, we present a 70-year-old non-smoking woman diagnosed with metastatic lung adenocarcinoma harboring an EGFR exon 19 deletion, who had received afatinib plus bevacizumab as the first-line therapy and almonertinib plus bevacizumab as the second-line therapy. Then the patient underwent osimertinib and bevacizumab as the third-line therapy. After 5-month treatment, the patient developed myalgia, muscular weakness, and tea-colored urine. The muscle strength grade of both the upper and lower limbs was III, and no other abnormalities were found. Serum creatine kinase (CK) and myoglobin (Mb) levels increased to 1,470 IU/L and 616.5 ng/mL. The patient also developed acute renal insufficiency, hyperuricemia, metabolic acidosis, and electrolyte disturbances. All symptoms were improved following the withdrawal of osimertinib. As a result, the patient was diagnosed with osimertinib-associated rhabdomyolysis.Conclusions: This is the first report of osimertinib-associated RM during the treatment of a lung adenocarcinoma patient. Although osimertinib-associated RM is rare, it is worthy of clinical attention in clinical practice, especially in patients receiving osimertinib plus bevacizumab. Once developed myalgia, muscular weakness and tea-colored urine, laboratory tests including serum creatine kinase (CK) and myoglobin (Mb) levels must be done, also osimertinib should be timely withdrawn to identify the cause.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rhabdomyolysis in a patient with advanced lung cancer treated with osimertinib: a case report

Li¹,

Liu²,

Zhao³

et al. 2023

Transl Lung Cancer Res

View full text Add to dashboard Cite

show abstract

“…One 2020 case series described four cases of myositis in patients treated with osimertinib. 4 Two of these patients had mild symptoms, two were identified after CPK monitoring was implemented as screening. All cases were initially Common Terminology Criteria for Adverse Event grade 1 to 2, with one patient later developing grade 4 elevation in CPK (2511 U/liter) without associated symptoms.…”

Section: Discussionmentioning

confidence: 99%

Life-Threatening Myositis in a Patient With EGFR-Mutated NSCLC on Osimertinib: Case Report

Crowley

Fitzgerald

Bhardwaj

et al. 2022

JTO Clinical and Research Reports

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Osimertinib is the standard of care for the first-line treatment of EGFR -mutated NSCLC. We report a case of a 52-year-old woman who developed life-threatening myopathy because of treatment with osimertinib. Limited instances of myositis have been previously reported in the literature; however, none have resulted in life-threatening oropharyngeal and respiratory muscle weakness as seen in this case. Care should be taken in administering osimertinib concurrently with other medications metabolized by the CYP3A4 system, and ongoing work to identify patients at risk for severe reactions is necessary. The use of routine creatinine phosphokinase monitoring should be considered as part of oncologic management.

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Metabolism and pharmacokinetic study of deuterated osimertinib

Zhan

Bao

et al. 2023

Biopharm & Drug Disp

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Osimertinib is a highly selective third‐generation irreversible inhibitor of epidermal growth factor receptor mutant, which can be utilized to treat non‐small cell lung cancer. As the substrate of cytochrome P450 enzyme, it is mainly metabolized by the CYP3A enzyme in humans. Among the metabolites produced by osimertinib, AZ5104, and AZ7550, which are demethylated that is most vital. Nowadays, deuteration is a new design approach for several drugs. This popular strategy is deemed to improve the pharmacokinetic characteristics of the original drugs. Therefore, in this study the metabolism profiles of osimertinib and its deuterated compound (osimertinib‐d3) in liver microsomes and human recombinant cytochrome P450 isoenzymes and the pharmacokinetics in rats and humans were compared. After deuteration, its kinetic isotope effect greatly inhibited the metabolic pathway that produces AZ5104. The plasma concentration of the key metabolite AZ5104 of osimertinib‐d3 in rats and humans decreased significantly compared with that of the osimertinib. This phenomenon was consistent with the results of the metabolism studies in vitro. In addition, the in vivo results indicated that osimertinib‐d3 had higher systemic exposure (AUC) and peak concentration (Cmax) compared with the osimertinib in rats and human body.

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Myositis – A common but underreported adverse effect of osimertinib: Case series and review of the literature

Cited by 9 publications

References 16 publications

Rhabdomyolysis in a patient with advanced lung cancer treated with osimertinib: a case report

Rhabdomyolysis in a patient with advanced lung cancer treated with osimertinib: a case report

Life-Threatening Myositis in a Patient With EGFR-Mutated NSCLC on Osimertinib: Case Report

Metabolism and pharmacokinetic study of deuterated osimertinib

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