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Background: Androgen deprivation therapy (ADT) combined with apalutamide, abiraterone acetate plus prednisone, enzalutamide, or docetaxel are the standard treatments for advanced castration-sensitive prostate cancer (CSPC). We investigated ADT-free alternatives for advanced CSPC. Patients and methods: LACOG 0415 is a phase 2, open-label, non-comparative, randomized trial. Patients with advanced CSPC were randomized (1:1:1) to receive goserelin plus abiraterone acetate and prednisone (ADT plus AAP arm), apalutamide (APA arm), or apalutamide plus abiraterone acetate and prednisone (APA plus AAP arm). The primary endpoint was the proportion of patients with PSA of 0.2 ng/mL at week 25 in the modified intentionto-treat population. Safety analyses were performed in all patients with at least one dose of the study drug. Results: Of 128 randomized patients, 120 patients were evaluable for PSA response at week 25; 17.2% had a high-risk biochemical recurrence, 8.6% had locally advanced disease, and 74.2% had distant metastases. At week 25, PSA of 0.2 ng/mL was observed in 75.6% (95%CI 59.7%e87.6%), 60.0% (95%CI 43.3%e75.1%), and 79.5% (95%CI 63.5%e90.7%) of patients in ADT plus AAP, APA, and APA plus AAP arms, respectively. PSA decline of !80% was observed in 100%, 90.0%, and 97.4%, respectively. Grade 3e4 AEs were observed in 31.0%, 21.4% and 36.4%, respectively. Testosterone levels increased significantly in the APA arm and decreased significantly in ADT plus AAP and APA plus AAP arms. Conclusions: ADT-free alternatives provide a high PSA response in advanced CSPC, although the APA arm did not reach the expected rate of PSA of 0.2 ng/mL at week 25. These results warrant further investigation of ADT-free treatments as alternatives in advanced CSPC. Source study registration: ClinicalTrials.gov NCT02867020.

TPS14 Background: Penile squamous cell carcinoma (PSCC) is an uncommon malignancy which accounts for 2,300 new cases and 400 deaths annually worldwide. However, in low-income countries from South America, Asia and Africa, incidence corresponds to 10-20% of all malignancies in men. Approximately 4% of PSCC patients present with metastatic disease at diagnosis. Also, even if diagnosed in early stages (localized disease), around 30% of patients will recur. No improvements have been achieved over the last three decades in platinum-based chemotherapy, which remains the standard-of-care; objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) are currently at 20-30%, 3-4 months and 7-15 months, respectively. HPV16 is the most important known risk factor for PSCC. Favorable results have been achieved with Pembrolizumab in other HPV-associated cancers, such as cervical and oropharyngeal cancer. HERCULES (LACOG 0218) aims to evaluate the efficacy of pembrolizumab combined with platinum-based chemotherapy as first-line treatment in advanced PSCC. Methods: HERCULES is a phase 2, single-arm, multicentric trial evaluating patients with histologically proven PSCC and metastatic disease (de novo or recurrent); or recurrent locally advanced disease not amenable to curative-intent therapy; or TanyN3M0 or T4NanyM0 (stage IV – AJCC 8th ed) not amenable to curative-intent therapy. Additional inclusion criteria were ECOG PS 0–1; measurable disease by RECIST 1.1; no prior systemic therapy for recurrent or metastatic disease (however, patients progressing after 12 months of neo/adjuvant chemotherapy completion are allowed). The primary endpoint is ORR up to week 24. Secondary endpoints are OS, PFS, clinical benefit rate, immune related response criteria, quality of life, safety, and predictive biomarkers of response/survival. Eligible subjects receive 5-FU 1000mg/m²/day IV D1-D4, cisplatin 70mg/m² or carboplatin AUC 5 IV D1 plus pembrolizumab 200mg IV D1 at each 3-week (Q3W) dosing cycle for 6 cycles, followed by Pembrolizumab 200mg IV Q3W maintenance. Patients without disease progression are allowed to continue pembrolizumab monotherapy until completing 34 cycles, disease progression or unacceptable toxicity, whichever comes first. Tumor evaluations are performed every 6 weeks until week 24. Sample size was calculated as 33 patients to detect an increase in ORR from 20% to 40% up to week 24 with 78.5% power and considering 10% drop-out. From Aug 2020 to Jul 2022, 33 patients were enrolled in 11 Brazilian research sites. Results are expected in 2023. NCT04224740. Clinical trial information: NCT04224740 .

BACKGROUNDHealthy lifestyle is capable of positively modifying the survival of breast cancer(BC) patients. We aimed to evaluate how physician's lifestyle in uences on the prescription of healthy habits to BC patients. METHODSAn online questionnaire to evaluate physician lifestyle and prescription of healthy habits to BC patients was developed and circulated by e-mail to physicians dedicated to treat BC patients. A multivariate Poisson regression analysis assessed which factors of physician lifestyle could in uence on prescription of healthy habits. RESULTSA total of 267 physicians answered the questionnaire from October to November 2018. In terms of physician lifestyle, 228(85.4%) had healthy eating habits and 236(88.4%) practiced physical activity.Overall, 84.3% of the physicians advised their BC patients on the importance of lifestyle modi cation. Physicians who did not exercise regularly have a higher chance of not advising for health lifestyle (RR 2.48; p=0.0265) as opposite to physicians ≥50 years-old (RR 0.37; p=0.0118). Obesity treatment and management was performed by 45.3% of physicians. Being a breast surgeon (RR 1.29; p=0.0025) or radiation oncologists (RR 1.82; p=0.0025) were associated with not performing obesity treatment and management. About 53.4% of physicians referred overweight or obese patients to a dietitian and/or endocrinologist. Male gender (RR 1.35; p=0.0296), breast surgeons (RR 1.99; p=0.0001) and clinical practice in public health system (RR 1.53; p=0.0012) were associated with not referring as opposed to physicians ≥50 years-old (RR 0.46; p=0.0005). CONCLUSIONIn general physicians treating BC patients have a healthy lifestyle. Only half of BC patients' physicians treat obesity or refer these patients to specialist which in this case may impact BC patient's outcome. Novelty & Impact StatementsA healthy lifestyle has been shown to have a positive impact on the quality of life, risk of recurrence, and overall survival in breast cancer. Physicians play an important role in encouraging their patients to lifestyle modi cation. LACOG 1218 survey identi ed that physicians treating BC patients have a healthy lifestyle and physician`s lifestyle in uences on the prescription of healthy habits to BC patients. Thus, strategies to engage physicians in healthier behaviors should be developed.

Conclusions:The results of our study, albeit with limitations related to the retrospective nature and the limited number of dMMR cases, might indicate a correlation between microsatellite instability and little or no response to preoperative chemoradiotherapy. It would be useful to analyze the data prospectively and further evaluate MMR as a predictor of response to combined chemo-radiotherapy.Legal entity responsible for the study: The authors.

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