No abstract

On March 23, 2022, the United States Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, also known as 177Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. The recommended 177Lu-PSMA-617 dose is 7.4 gigabecquerels (GBq; 200 mCi) intravenously every 6 weeks for up to 6 doses, or until disease progression or unacceptable toxicity. The FDA granted traditional approval based on VISION (NCT03511664), which was a randomized (2:1), multicenter, open-label trial that assessed the efficacy and safety of 177Lu-PSMA-617 plus best standard of care (BSoC) (n=551) or BSoC alone (n=280) in men with progressive, PSMA-positive mCRPC. Patients were required to have received ≥1 androgen receptor pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens. There was a statistically significant and clinically meaningful improvement in overall survival (OS) with a median OS of 15.3 months in the 177Lu-PSMA-617 plus BSoC arm and 11.3 months in the BSoC arm, respectively (Hazard ratio: 0.62, 95% CI: 0.52, 0.74, p<0.001). The most common adverse reactions (≥20%) occurring at a higher incidence in patients receiving 177Lu-PSMA-617 were fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in ≥30% of patients receiving 177Lu-PSMA-617 were decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium. This article summarizes the FDA review of data supporting traditional approval of 177Lu-PSMA-617 for this indication.

Although the role of radiation therapy and chemotherapy in primary central nervous system lymphoma (PCNSL) has evolved considerably over the past decade, the application of treatment modalities in the community has not been evaluated. We analyzed the use of chemotherapy, radiation therapy, and associated overall survival, among 9165 HIV-negative PCSNL cases reported to the US National Cancer Database in 2004-2013. During this time, the proportion of patients receiving chemotherapy significantly increased from 65.6% to 78.8% ( for trend <.0001), whereas the proportion receiving radiation therapy decreased from 37.6% to 18.8% ( < .0001). Adjusting for the varying distribution of clinical and sociodemographic characteristics by type of treating facility, the risk of not receiving chemotherapy was significantly lower in academic/research cancer programs compared with community programs (adjusted relative risk, 0.69; 95% confidence interval [CI], 0.62-0.76; < .0001). Furthermore, omission of chemotherapy was associated with increasing age, comorbidities, black race, and indicators of poor socioeconomic status. Overall survival at 3 years was 37.7% (95% CI, 36.6-38.8) and ranged from 14.1% for patients treated with radiation therapy alone to 51.8% for those who received multiagent chemotherapy. There was evidence of improved survival over time ( for trend =.0002). The disparities in application of chemotherapy for PCNSL underscore the need to provide access to expert management for this rare disease and improve safe delivery of systemic treatment in the community setting, where most older patients receive their care.