68Ga-PSMA-11 NDA Approval: A Novel and Successful Academic Partnership.

The University of California Los Angeles (UCLA) and University of California San Francisco (UCSF) codeveloped 68Ga-PSMA-11 by conducting a bicentric pivotal phase 3 clinical trial for PET imaging for prostate cancer. On December 1, 2020, 2 separate new drug applications (NDAs) submitted by each institution (NDA 212642 for UCLA and NDA 212643 for UCSF) were approved by the Food and Drug Administration as the first drug for PET imaging of prostate-specific membrane antigen (PSMA)-positive lesions in men with prostate cancer. This article briefly describes the background, clinical development, regulatory approach, and regulatory process for NDA filing and approval. In the second part of this article, key chemistry, manufacturing, and controls (CMC) information is provided to facilitate abbreviated new drug application (ANDA) submission.

Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial.

IMPORTANCE: In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging. OBJECTIVE: To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard. MAIN OUTCOMES AND MEASURES: Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety. RESULTS: A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients. CONCLUSIONS AND RELEVANCE: Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.

Salivary morbidity and quality of life following radioactive iodine for well-differentiated thyroid cancer.

OBJECTIVE: Determine the prevalence of sialadenitis in a group of patients treated with radioactive iodine (RAI) for well-differentiated thyroid cancer and assess whether RAI treatment is associated with a reduction in swallowing-related or global head and neck quality of life. STUDY DESIGN: Retrospective self-administered questionnaire study. SETTING: Academic, tertiary care, National Cancer Institute-designated cancer center. SUBJECTS AND METHODS: Surviving patients seen for well-differentiated thyroid cancer were identified by review of the cancer center registry. Patients were mailed a baseline questionnaire, the M. D. Anderson Dysphagia Inventory (MDADI), the University of Washington Quality of Life Questionnaire (UW-QOL), and the Xerostomia-Related Quality of Life Scale (XeQOLS). RESULTS: The study included 121 women and 24 men, with a mean age of 52 years. Radioactive iodine exposure was correlated with an increase in sialadenitis and was dose dependent (R (2) = 0.335, P < .001). Sialadenitis was 2.47 times more likely to occur in patients who received greater than 150 mCi when compared with those who received less than 150 mCi (P = .04). Radioactive iodine exposure of over 150 mCi was also associated with a reduction in the recreation domain of the UW-QOL (P = .04), the daily swallowing domain of the MDADI (P = .02), and the psychological/personal, pain, and social domains of the XeQOLS (P = .03, .03, and .04, respectively). CONCLUSION: Patients treated with RAI exhibited an increased risk for sialadenitis as well as a reduction in swallowing-related and global head and neck quality of life. Our findings suggest these patients should be screened for salivary morbidity and may benefit from both pre-RAI prophylaxis and post-RAI intervention.