Impact of bleomycin shortage in patients with advanced testicular non-seminoma germ-cell tumors: A middle-income country cancer center experience.

Abstract

623 Background: Standard of care for advanced NSGCTs is BEP (bleomycin, etoposide, cisplatin). Social, epidemiologic and economic factors can impact drug availability. In our institution, the COVID-19 pandemic limited accessibility to several antineoplastic drugs, including bleomycin. This analysis describes the frequency of BEP modifications and its impact in prognosis of intermediate (IP) and poor (PP) NSGCT treated at the National Cancer Institute in Mexico. Methods: Retrospective observational study performed from 2018 to 2022. Clinical characteristics and chemotherapy modifications were retrieved from electronic charts. Survival curves were built with Kaplan-Meier method and compared log-rank test to demonstrate effects of different clinicopathological variables on survival. Statistically significant variables in univariate analysis were included in multivariate Cox regression. Results: 179 patients included. Median age 23 (16-56). 33% had IP and 66% PP; 32% had non-pulmonary visceral metastases (NPVM). 60% had at least one dose modification. Median dose of bleomycin was 67.5 IU (IQR, IU 0-90) per cycle. 42% of patients received the full-dose of bleomycin (Bleo360) dose. 55.8% of bleomycin modifications were due to drug shortage. 88% who received Bleo360 didn´t have other chemotherapy drug modifications (p<.001). Median Progression Free Survival (mPFS) was 17.4 months (95% Confidence Interval (CI), 11.8-23.1). Median Overall Survival (mOS) was 73.6 months (95% CI, 20.6-126.7). Univariate and multivariate analysis are described in the table. Conclusions: Oncology drug shortages may have serious consequences for patient’s survival. In our cohort the dose-modifications of bleomycin had a deleterious impact in the survival of IP/PP NSGCTs patients. Policy modifications and stakeholders awareness is paramount to decrease shortage of “vintage” oncological therapies. Univariate and multivariate analysis. Univariate Multivariate Variable PFS HR(IC 95%) p OS HR(IC 95%) p PFS HR(IC 95%) p OS HR(IC 95%) p IPPP 0.34(0.21-0.56) <0.0001 0.3(0.2-0.5) 0.0001 Ref.2.4(1.4-4.2) 0.002 Ref.2.8(1.5-5.5) 0.002 NPVMNoYes 0.53(0.36-0.78) 0.001 0.5(0.4- 0.9) 0.011 Ref.1.3(0.9-2) 0.2 Ref.1.1(0.7-1.9) 0.6 Bleo360YesNo 0.6(0.66-0.98) 0.04 0.63(0.39-1.0) 0.06 Ref.1.3(0.9-2.0) 0.1 Ref.1.3(0.8-2.1) 0.3 Log Tumor MarkerFavorableUnfavorable 0.51(0.30-0.84) 0.009 Ref.2.1(1.2-3.7) 0.008 Ref.1.6(0.9-2.9) 0.1