Background: Platinum agents induce DNA crosslinking and cause accumulation of genotoxic stress, which leads to immune activation via IFN-γ signaling, making the combination with nivolumab (PD-1 antibody) an attractive strategy to enhance the benefit of either agent alone in metastatic triple-negative breast cancer (mTNBC). Methods: In this phase II open-label, investigator-initiated, multicenter trial, patients with unresectable locally advanced or mTNBC treated with 0-1 prior lines of chemotherapy in the metastatic setting were randomized 1:1 to carboplatin (AUC 6) with or without nivolumab (360 mg) IV every 3 weeks. Stratification factors included: germline BRCA (gBRCA) status, prior neo/adjuvant platinum, and number of prior lines of metastatic therapy. After approval of PD-L1 inhibition for mTNBC, the study was amended to include first-line mTNBC only and PD-L1 status was added as a stratification factor. Patients randomized to carboplatin alone were allowed to crossover at progression to receive nivolumab (+ nab-paclitaxel post-amendment). The primary objective was to compare progression-free survival (PFS) per RECIST 1.1 criteria of carboplatin with or without nivolumab in first-line mTNBC in the intent-to-treat (ITT) population. Key secondary objectives were objective response rate (ORR), overall survival (OS), clinical benefit rate, and duration and time to objective response. PD-L1 status was confirmed centrally using the SP142 Ventana assay (positive, ≥1% IC). Paired research biopsies at baseline, on-treatment and at progression were performed, if safely accessible. The trial closed to accrual prior to reaching target accrual due to approval of PD-1 inhibition in combination with platinum-based chemotherapy for PD-L1+ mTNBC. Results: Between 1/30/2018 and 12/9/2020, 78 patients enrolled. Three patients did not receive protocol treatment, and the safety analysis was conducted among the 75 that received any treatment; 37 received carboplatin + nivolumab (Arm A), 38 received carboplatin alone (Arm B). Median age was 59.1 yrs (range: 25.4-75.8). Four patients (5.3%) had a known gBRCA1/2 mutation. Sixty-two (82.7%) patients received 0 prior lines (ITT population) and 13 (17.3%) 1 prior line of metastatic therapy. Sixty-seven patients (89.3%) experienced any grade ≥2 treatment-related adverse event (AE). The most frequent AE were platelet count decrease (n=40; 53.3%), anemia (n=36; 48.0%), neutrophil count decrease (n=33; 44.0%) and fatigue (n=24; 32.0%). Grade 3/4 AE were observed in 46 (61.3%) patients, and there was one grade 5 AE (COVID19 pneumonia). Any grade ≥2 immune-related AE (irAE) were observed in 25 of the 37 (67.6%) patients treated with carboplatin + nivolumab. Grade 3/4 irAE were observed in 11 (29.7%) patients. In the ITT population (32 on Arm A; 30 on Arm B), median PFS was 4.2 months with carboplatin + nivolumab, and 5.5 months with carboplatin (stratified HR 0.98, 95% CI [0.51 - 1.88]; p=0.95). ORR was 25% vs. 23.3%, respectively. At a median follow-up of 23.5 months, median OS was 17.5 months vs. 10.7 months (stratified HR 0.63, 95% CI [0.32 - 1.24]; p=0.18). In patients with PD-L1+ mTNBC (13 on Arm A; 11 on Arm B), median PFS was 8.3 months and 4.7 months, respectively (stratified HR 0.63, 95% CI [0.21 - 1.89]; p=0.41). ORR was 23.1% vs. 27.3%, respectively. Median OS was 17.5 months vs. 9.6 months (stratified HR 0.59, 95% CI [0.20 - 1.75]; p=0.34). Conclusions: Addition of nivolumab to carboplatin in patients with previously untreated mTNBC, unselected by PD-L1 status, did not significantly improve PFS. A trend toward improved PFS and OS was observed in patients with PD-L1+ mTNBC. Tissue, blood and intestinal microbiome biomarker analyses are planned; bulk tumor and single-cell sequencing, and TCR sequencing in peripheral blood are ongoing. Clinical trial information: NCT03414684. Citation Format: Ana C Garrido-Castro, Noah Graham, Kevin Bi, Jihye Park, Jingxin Fu, Tanya Keenan, Edward Thomas Richardson, Ricardo Pastorello, Paulina Lange, Victoria Attaya, Robert Wesolowski, Natalie Sinclair, Zarah Lucas, Steve Lo, Nadine Tung, Meredith Faggen, Peter A Kaufman, Caroline C Block, Fred Briccetti, Madhavi Toke, Wendy Chen, Kai Wucherpfennig, Sascha Marx, Ye Tian, Judith Agudo, Jennifer L Guerriero, Stuart Schnitt, Nancy U Lin, Eric P Winer, Elizabeth A Mittendorf, Nabihah Tayob, Eliezer Van Allen, Sara M Tolaney. A randomized phase II trial of carboplatin with or without nivolumab in metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-18.

Objective: To describe the clinical characteristics of patients diagnosed with hepatocellular cancer admitted at the Philippine Background: Hepatocellular carcinoma (HCC) is the third leading site of cancer in the Philippines. Although risk factors for HCC are already established, significance of risk factors may vary among regions. Diabetes has also not been examined as a risk factor among Filipinos. Methodology: This is a descriptive study with data collection done through chart review. All charts with the diagnosis of hepatocellular carcinoma admitted from 2001 to 2006 were retrieved from the Medical Records Section. Participants included all adult hepatocellular carcinoma patients, diagnosed with HCC either by: (1) biopsy or (2) mass > 2cm and elevated -fetoprotein >200. Demographic data, risk factors, and laboratory exams were collated. Descriptive statistics were generated using SPSS 15.0.Results: Two hundred twenty two patients were included in the study. Males outnumbered females (3.5:1). Majority were older than 50 years old. The most common symptom is abdominal pain. Two thirds had a history of drinking alcohol. Almost half were smokers. Thirty eight patients (40.0%) had previous hepatitis B and 66 patients (52.3%) had chronic Hepatitis B. Only 3 (6.2%) patients had hepatitis C infection. Two thirds had no evidence of cirrhosis. Thirteen percent of the population had diabetes mellitus while 20% of the HBsAg-negative patients had diabetes mellitus. Eighty seven percent were in the advanced stage and 11.7% were terminal stage. Conclusion:The most common risk factors for HCC are still hepatitis B infection and alcohol drinking. Diabetes mellitus deserves to be investigated as an important contributing factor to the development of HCC, especially in HBsAg-negative patients. Most patients belonged to late stages of the disease but a selection bias is recognized. Our study indicates the need for screening patients at risk so early-stage disease can be detected.

Importance. Laryngeal cancer infrequently results in distant metastases, but metastasis to skeletal muscle is extremely uncommon. Observations. A 55-year-old male presenting with progressive dyspnea and hoarseness was found to have Stage IVA T4aN2cM0 laryngeal cancer and eventually underwent total laryngectomy. Before the patient could be started on adjuvant chemoradiation, the patient developed masses on both thighs. Biopsy revealed metastatic squamous cell carcinoma consistent with the primary laryngeal cancer. He was offered palliative chemotherapy; however, he developed new soft tissue masses to the left of his stoma and in the prevertebral area one week later. He also had new cervical and supraclavicular nodes and a pathological compression fracture of L3. Patient died within 4 months of diagnosis. Conclusions. Distant metastasis such as skeletal metastasis portends a poor prognosis. Further studies are required to determine the best course of treatment in these patients.

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