A 74-year-old female with metastatic triple-negative breast cancer was admitted to the acute care hospital after several ground-level falls and a two-week history of bilateral lower extremity weakness with foot drop, numbness, and tingling. She was on ladiratuzumab vedotin (SGN-LIV1A) and pembrolizumab for four months prior to cancer treatment. Lumbar and sacral imaging studies did not identify neoplastic invasion into the bone or lumbosacral plexus. Electrodiagnostic findings suggested bilateral lumbosacral plexopathy (L3-S1). In the setting of rapid functional decline, medications were reviewed, and SGN-LIV1A was held. On initial evaluation, she required significant assistance with ambulation, transfers, and activities of daily living (ADLs). She remained off SGN-LIV1A and was discharged to acute inpatient rehabilitation. One month following discharge from acute inpatient rehabilitation, she exhibited improvements in right lower extremity strength and foot drop and progressed to modified-independent with ADLs, ambulating with a walker. In a discussion between cancer rehabilitation and oncology with consideration of the timing of presentation, distribution of symptoms, nerve conduction study and electromyography (NCS/EMG) findings, and improvement after SGN-LIV1A discontinuation, the patient was diagnosed with lumbosacral plexopathy from SGN-LIV1A administration. This is the only reported case of lumbosacral plexopathy secondary to SGN-LIV1A and addresses the importance of early consultation with cancer rehabilitation to address sequelae stemming from cancer therapy.
Introduction
Metastatic triple-negative breast cancer (mTNBC) lacks the expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) [1]. Because mTNBC is nonresponsive to endocrine or molecular targeted therapeutics, chemotherapy is currently the first-line treatment [2]. However, mTNBC is generally nonresponsive to chemotherapy, resulting in a poor prognosis with a median overall survival rate of less than two years [3].
Interestingly, 90% of all breast tumors have been shown to express high levels of LIV-1, a transmembrane zinc transporter linked to metastatic progression. Ladiratuzumab vedotin (SGN-LIV1A) is an antibody-drug conjugate (ADC) that utilizes a monoclonal antibody to target LIV-1, resulting in the internalization of conjugated microtubule inhibitor monomethyl auristatin E (MMAE) by mTNBC cells [1,3,4]. Preliminary findings from a recent phase I trial involving mTNBC patients indicate a 32% overall response rate to SGN-LIV1A, prompting further investigation of the ADC as a potential mTNBC therapeutic [3]. Although promising, the adverse effect profile of SGN-LIV1A remains relatively unknown. The drug, SGN-LIV1A, is still under clinical trial and has not yet received United States Food and Drug Administration approval for the treatment of mTNBC. ClinicalTrials.gov identifier: NCT03310957.
We report a unique case of a patient with mTNBC who developed lumbosacral plexopathy while taking SGN-LIV1A. Lumbosacral plexopathy is an injury to the nerves that make up the lumbar and sacral plexus and is characterized by motor and sensory dysfunction of the lower extremities [5]. Lumbosacral plexopathy is a difficult condition to diagnose and treat and can lead to significant functional impairment and morbidity [6]. Early diagnosis and intervention are essential for the preservation of function in patients diagnosed with lumbosacral plexopathy [5]. This case addresses the role of inpatient rehabilitation and importance of early consultation with cancer rehabilitation physicians to address sequelae stemming from cancer therapy.
This case report was previously presented as a poster presentation at the AAPM&R Annual Conference in 2022 [7].
Case Presentation
A 74-year-old female diagnosed with mTNBC presented with a primary right breast tumor 20-50 mm in size with associated metastases to four to nine lymph nodes and the liver (T2N2M1). She was admitted to the acute care hospital for a two-week history of bilateral lower extremity weakness (right greater than left) with associated right foot drop and bilateral distal upper and lower extremity numbness and tingling. She had been taking SGN-LIV1A and pembrolizumab for five cycles over four months per the Seattle Genetics Clinical Protocol [8]. SGN-LIV1A was held throughout cycle 6 due to the aforementioned symptoms. Prior to her admission, the patient was initially treated in an outpatient setting with steroids without improvement and evaluated by outpatient cancer rehabilitation. She was prescribed outpatient physical and occupational therapy but was eventually admitted to an acute care hospital under observation due to rapid functional decline and several ground-level falls. Inpatient Physical Medicine & Rehabilitation (PM&R)/Cancer Rehabilitation were consulted for suspicion of lumbosacral plexopathy secondary to SGN-LIV1A use.
Physical examination showed loss of sensation to light touch in bilateral plantar feet (L>R) and fingertips. Strength testing was significant for 4+/5 right hip flexion, 4+/5 right knee extension, 4/5 right ankle dorsiflexion, and 3/5 right and 4+/5 left extensor hallucis longus extension. On initial physical and occupational therapy evaluations, the patient was below the independent baseline level of function, as she required moderate assistance and a front-wheeled walker (FWW) for ambulation, transfers, and activities of daily living (ADLs).
Outpatient electrodiagnostic findings suggested bilateral lumbosacral plexopathy, with dysfunction in the right L4/5 myotome being the most severe (Tables 1, 2). Of note, she was found to have Baastrup’s disease (degenerative changes leading to decreased space between adjacent lumbar spinous processes) around the L4/5 region; however, this did not fully explain her symptoms or exam findings. Brain MRI did not identify abnormalities. Lumbar MRI was significant for degenerative changes in the L3-4 and L4-5 interspinous tissues with moderate spinal canal and bilateral neural foraminal stenosis, consistent with the patient’s Baastrup’s disease. Subsequent nuclear medicine bone scan did not identify any bone metastases (Figure 1). No evidence of neoplastic invasion into the lumbosacral plexus was found on sacrum MRI with and without contrast (Figure 2).
Source : Cureus
