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5018 Background: The PARP-inhibitor olaparib is approved for mCRPC patients (pts) with deleterious germline or somatic homologous recombination repair gene mutations (HRRm). PARP1 interacts with androgen signaling, and castration-resistant tumor cells exhibit increased PARP1 activity. Preclinically PARP1-inhibition synergizes with androgen receptor (AR) targeted therapy. BRCAAway is a biomarker selected, randomized, open-label, multicenter phase 2 trial evaluating efficacy of targeting AR vs PARP vs combination in first line mCRPC patients with germline and/or somatic HRRm in BRCA1, BRCA2, or ATM. Methods: Eligible mCRPC pts underwent tumor next generation sequencing and germline testing. Pts with inactivating BRCA1, BRCA2 and/or ATM alterations were randomized 1:1:1 to Arm 1 abiraterone (1000 mg daily) + prednisone (5mg bid) (Abi/pred), Arm 2 olaparib (300 mg bid) or Arm 3 olaparib + Abi/pred. The primary end point is progression-free survival (PFS) analyzed using Kaplan-Meier estimates and Cox regression. Secondary endpoints include measurable disease response rate (RR) by RECIST, PSA-RR, undetectable PSA (≤ 0.2 ng/ml) and toxicity. Arms 1 and 2 pts were allowed to cross over at progression. Pts with other HRRm were treated with olaparib; Arm 4 (ongoing). Results: 161 pts were registered and had NGS testing; 60 pts were randomized to Arms 1-3; to date 59 are evaluable for toxicity and 53 are evaluable for PFS. Baseline median age 67 (range 42-85) years; 54 pts were White, 6 were Black; sites of disease: bone only (n=31), soft tissue only (n=18), bone and soft tissue (n=10); median PSA 14.61 ng/ml (range 0.15-4036.8). Mutational status: BRCA1 only n = 2, BRCA2 only n = 39, ATM only n = 8, and > 1 HRRm n = 11. 34 pts had germline and 26 had somatic mutations. Median (range) follow-up time: 8.3 (0.8, 33.3), 12.2 (2.7, 21.8) and 16.8 (2.9, 41.7) months in Arms 1, 2 and 3. 43 pts had treatment-related adverse events; most common were fatigue (23 pts; 1 Grade (G) 3, 22 G1/2), nausea (17 pts, G1/2), and anemia (9 pts, 2 G3, 7 G1/2). ≥50% PSA decline was 79%, 67%, and 85% of pts in Arms 1, 2, and 3, respectively. Median PSA nadir (ng/mL) (95% CI) Arms 1-3: 2.17 (0.44, 49.27), 3.10 (0.83, 12.01), and 0.50 (0.10, 2.13), respectively. Undetectable PSA, median PFS, and 12-month PFS by Arm are listed in the table. Conclusions: In mCRPC pts with inactivating BRCA1, BRCA2 and/or ATM alterations Abi/pred + olaparib was well tolerated and resulted in longer PFS and better PSA response vs either agent alone. Clinical trial information: NCT03012321. [Table: see text]

Study Design Survey Objective In March of 2020, an original study by Louie et al investigated the impact of COVID-19 on 902 spine surgeons internationally. Since then, due to varying government responses and public health initiatives to the pandemic, individual countries and regions of the world have been affected differently. Therefore, this follow-up study aimed to assess how the COVID-19 impact on spine surgeons has changed 1 year later. Methods A repeat, multi-dimensional, 90-item survey written in English was distributed to spine surgeons worldwide via email to the AO Spine membership who agreed to receive surveys. Questions were categorized into the following domains: demographics, COVID-19 observations, preparedness, personal impact, patient care, and future perceptions. Results Basic respondent demographics, such as gender, age, home demographics, medical comorbidities, practice type, and years since training completion, were similar to those of the original 2020 survey. Significant differences between groups included reasons for COVID testing, opinions of media coverage, hospital unemployment, likelihood to be performing elective surgery, percentage of cases cancelled, percentage of personal income, sick leave, personal time allocation, stress coping mechanisms, and the belief that future guidelines were needed (P<.05). Conclusion Compared to baseline results collected at the beginning of the COVID-19 pandemic in 2020, significant differences in various domains related to COVID-19 perceptions, hospital preparedness, practice impact, personal impact, and future perceptions have developed. Follow-up assessment of spine surgeons has further indicated that telemedicine and virtual education are mainstays. Such findings may help to inform and manage expectations and responses to any future outbreaks.