4CPS-205 Alectinib for ALK-positive uterine leiomyosarcomal: sustained response after treatment resistance – a case report

<h3>Background and Importance</h3> Uterine leiomyosarcoma (uLMS) is a highly aggressive soft-tissue sarcoma with frequent metastatic relapse after surgery, in which chemotherapy offers limited efficacy in advanced cases. Alectinib, a second-generation ALK inhibitor approved for non-small-cell lung cancer, has shown potential benefits in ALK-rearranged non-lung tumours. <h3>Aim and Objectives</h3> A 57-year-old woman with a family history of cancer, diagnosed with uterine leiomyosarcoma in February 2018. She underwent hysterectomy, appendectomy, and resection of prevesical and peritoneal implants. Adjuvant chemotherapy with doxorubicin was completed by June 2018. <h3>Material and Methods</h3> A PET/CT scan in November 2018 revealed disease progression with pulmonary metastases. Over the following years, the patient received eight lines of treatment due to disease progression or adverse events (AEs), including: gemcitabine + paclitaxel, trabectedin, pazopanib, temozolomide, dacarbazine + gemcitabine, liposomal doxorubicin, eribulin, and letrozole. Genetic testing revealed no mutations in BRCA, NTRK, or PD-L1 expression. However, in March 2022, genotyping identified an ALK mutation, and alectinib therapy was subsequently recommended. <h3>Results</h3> Alectinib therapy was initiated in April 2022 at a dosage of 600 mg every 12 hours. Routine evaluations, including imaging scans and blood tests, monitored treatment effectiveness and safety. Medication was dispensed via the outpatient pharmacy unit, where hospital pharmacists also monitored for potential drug interactions and AEs. After three months, a PET/CT scan revealed a partial response with reduced tumour size and metastatic lesions. This therapeutic response remains ongoing. Mild adverse events occurred, including grade 1 constipation and a right-eye cataract. By October 2023, the patient developed a non-pruritic, photosensitivity-related rash, which was treated with topical corticosteroids. In March 2024, the patient experienced a recurrence of grade 1 skin toxicity. Dermatological evaluation led to a diagnosis of plaque psoriasis, for which topical corticosteroids and emollients were prescribed. No significant laboratory abnormalities were noted during treatment. <h3>Conclusion and Relevance</h3> In this case, alectinib has demonstrated effectiveness in managing uLMS with an ALK mutation after several lines of prior treatment. The patient has maintained a partial response to therapy since the initiation of alectinib, with no severe adverse events reported. However, further clinical studies are necessary to assess the broader efficacy of alectinib in this tumour type, as it remains an off-label use. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest