Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw.

Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, reduces skeletal-related events (SREs) and is approved for solid tumors with bone metastases. We studied long-term denosumab efficacy and safety because real-world data is scarce. This single-arm, single-center retrospective study included denosumab-treated breast cancer patients with bone metastases. Kaplan-Meier survival curves assessed exposure, SREs, osteonecrosis of the jaw (ONJ), and death. 132 patients were enrolled. The median denosumab exposure was 28.3 months (range 1.0-84.9). In the first year, 11.1% experienced SREs. This increased to 18.6% in the second, 21% in the third, and 35.1% in the fourth year and beyond. The median time to first on-study SRE has not been reached. 10 denosumab users (7.6%) developed ONJ. ONJ incidence was 0.9% in the first year, 6.2% in the second, 13.6% in the third, and 16.2% in subsequent years. The median time to first on-study ONJ has not been reached yet. Seven patients resumed denosumab after careful management of ONJ. Our data suggest that long-term treatment with denosumab may further prevent or postpone SREs at the cost of an increased risk of ONJ. The majority of patients who resumed denosumab did not experience a recurrence of ONJ.

Real-life analysis of neoadjuvant-therapy-associated benefits for pathological complete response and survival in early breast cancer patients - role of trastuzumab in HER2+ BC and platinum in TNBC.

Background: Neoadjuvant therapy, which aims to achieve a pathological complete response (pCR) for better overall survival (OS) has several advantages for patients with early breast cancer (eBC) and subtypes of HER2-positive (HER2+) and triple-negative breast cancer (TNBC). However, there has been no large-scale real-world investigation on the clinical outcomes associated with trastuzumab-based and platinum-based neoadjuvant treatments for patients with HER2+ and TNBC, respectively. Material and methods: Taiwan Cancer Registry and National Health Insurance Research Database were utilized in this study. Patients diagnosed with clinically lymph-node-positive (LN+) HER2+ or TNBC were identified for analysis. Logistic regression and Cox proportional hazard models were employed to estimate the adjusted odds ratios (aOR) of achieving pCR and adjusted hazard ratios (aHR) of overall survival associated with treatment agents, respectively. Results: A total of 1,178 HER2+ eBC and 354 early TNBC patients were identified, respectively. Neoadjuvant trastuzumab significantly increased the pCR rates by 3.87-fold among HER2+ patients. Trastuzumab-associated survival benefit was found in HER2+ patients who achieved pCR (aHR [95% CI]: 0.30 [0.11-0.84]) but not in those without pCR (1.13 [0.77-1.67]). Among the TNBC patients, platinum was associated with a 1.6-fold increased pCR rate; however, it did not improve OS regardless of pCR status. Conclusions: Trastuzumab improved pCR and OS for patients with HER2+ subtype. Using platinum agents for TNBC patients increased pCR rates but was not linked to better survival. Optimal neoadjuvant anti-HER2 therapy for patients with HER2+ eBC and the introduction of novel therapy for patients with TNBC should be considered.

Anaplastic Thyroid Cancer Successfully Treated With Radiation and Immunotherapy: A Case Report.

OBJECTIVE: Anaplastic thyroid cancer (ATC) is a rare thyroid cancer subtype with a devastating prognosis. Novel treatment strategies are under investigation to improve the survival of patients with ATC. METHODS: We present a case of recurrent ATC treated with a combination of radiation therapy (RT) and pembrolizumab, a programmed death-1 inhibitor, with a durable complete response. RESULTS: A 63-year-old woman underwent total thyroidectomy and left neck lymph node dissection and was diagnosed with papillary carcinoma in December, 2017. She received radioiodine in April, 2018. However, a left neck mass was noted in April, 2018 with biopsy demonstrating ATC with 95% positivity for programmed death-ligand 1 immunostaining. Positron emission tomography showed fluorodeoxyglucose uptake in the left thyroid bed and multiple lymph nodes in the left retropharyngeal, left neck, and right upper paratracheal areas. Hypofractionated RT for the recurrent areas was initiated in August,2018, and concomitant pembrolizumab was given 2 days after RT. A total of 10 cycles of pembrolizumab (2 mg/kg) were given every 3 weeks. The computed tomography scan after completion of RT and 3 cycles of pembrolizumab showed shrinkage of the neck lymph nodes. The serial follow-up computed tomography scans showed further shrinkage of the lymph nodes, and there was no recurrence of ATC as of October, 2020. CONCLUSION: We describe an ATC case successfully treated with a combination of RT and pembrolizumab with a durable response of 26 months and acceptable toxicities. This result warrants further investigation of this combination regimen in the treatment of ATC.