Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. HCC tumor development and treatment resistance are impacted by changes in the microenvironment of the hepatic immune system. Immunotherapy has the potential to improve response rates by overcoming immune tolerance mechanisms and strengthening anti-tumor activity in the tumor microenvironment. In this review, we characterize the impact of immunotherapy on outcomes of advanced HCC, as well as the active clinical trials evaluating novel combination immunotherapy strategies. In particular, we discuss the efficacy of atezolizumab and bevacizumab as demonstrated in the IMbrave150 study, which created a new standard of care for the front-line treatment of advanced HCC. However, there are multiple ongoing trials that may present additional front-line treatment options depending on their efficacy/toxicity results. Furthermore, the preliminary data on the application of chimeric antigen receptor (CAR-T) cell therapy for treatment of HCC suggests this may be a promising option for the future of advanced HCC treatment.
Dedifferentiated chondrosarcomas (DDCS) are aggressive tumors with poor outcomes. Treatment of localized DDCS is primarily surgical, though most patients present with unresectable or metastatic disease. Systemic treatment options for advanced DDCS are limited, and the benefits of chemotherapy in this patient population remain controversial. Among other systemic therapy options, there is emerging clinical evidence to support the use of immunotherapy in patients with advanced DDCS. However, studies regarding the efficacy of immunotherapy in advanced DDCS are limited. Here, we present the case of a patient with metastatic, programmed death-ligand 1 (PD-L1)-positive DDCS treated with pembrolizumab who showed a sustained complete response for 24 months after initiation of therapy. To our knowledge, this case represents one of few documented cases of metastatic chondrosarcoma with sustained response to immunotherapy. The impressive response seen with PD-L1 inhibition in our patient indicates that immunotherapy is a successful treatment option in a subset of DDCS patients, and further investigation is needed to identify potential responders to immunotherapy.
e16200 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Indoleamine-2,3-dioxygenase (IDO) is an intracellular enzyme expressed by HCC which helps to orchestrate immune suppression within the tumor microenvironment (TME) and may contribute to primary and acquired resistance of PD-(L)1 inhibitors. BMS-986205 is a novel oral drug that potently and selectively inhibits IDO1. This Phase I/II study is evaluating the safety and tolerability of the combination of BMS-986205 and nivolumab as first-line therapy in HCC. Methods: Patients (pts) ≥18y with untreated, unresectable/metastatic HCC received BMS-986205 in combination with nivolumab. A fixed dose of Nivolumab 240mg/m2 IV was administered on Day 1 of each 14-day cycle. BMS-986205 was an oral tablet administered daily; a total of two dose levels (50-100mg) were given to determine dose limiting toxicities (DLT) during the dose-escalation Phase I of the study. Safety was assessed using CTCAE v5.0 criteria, and efficacy was assessed by objective response rate (ORR) using RECIST v1.1 criteria. Secondary objectives included preliminary data on disease control rate (DCR), duration of response (DOR), ORR using immune RECIST criteria (iRECIST), progression free survival (PFS) and overall survival (OS). Results: Here we report the results of the dose escalation cohort. Eight pts were treated with median age 69y [60-76]; 75% male; and PS 0 (3 pts) or 1 (5 pts). Pts were White (62.5%), Asian (25%), and African American (12.5%). Six of 8 pts had underlying viral hepatitis (5 hepatitis C, 1 hepatitis B), and all pts were Child Pugh A at enrollment with median baseline alpha-fetoprotein (AFP) level 41.8 [3.8–917.2]; 4 pts received prior local therapies. A total of 91 cycles of therapy were administered; 2 pts received 27 and 43 cycles of treatment each. Six pts were evaluable for DLT; 2 pts were replaced for DLT assessment due to insufficient dose administered, unrelated to toxicity. No DLTs were observed at either the 50 or 100mg dose of BMS-986205. There were 24 treatment-related adverse events (TRAEs), 4 of which were Grade 3 events; there were no Grade 4-5 events. The most common TRAEs of all grades were AST elevation and ALT elevation in 3 pts, and diarrhea, maculopapular rash and increased alkaline phosphatase in 2 pts each. Grade 3 events were diarrhea and AST elevation (1 pt), and hyperglycemia and pancreatitis requiring treatment discontinuation (1 pt). Eight pts were evaluable for efficacy with best response of partial response in 1 pt (12.5%) and stable disease in 3 pts (37.5%), yielding a DCR of 50%. Median PFS was 8.5 weeks; median OS has not been reached. Conclusions: Combination BMS-986205 and nivolumab showed a manageable safety profile with durable benefit as 1st line therapy in a meaningful subset of patients with unresectable/metastatic HCC. Clinical trial information: NCT03695250.
776 Background: With an estimated six percent five-year survival, metastatic pancreatic adenocarcinoma is one of the most lethal cancers in the United States. Previously, treatments with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (G+A) have demonstrated improved overall survival versus gemcitabine alone. The purpose of this study is to compare institutional outcomes for the two regimens, FFX vs. G+A in metastatic pancreatic cancer. Methods: We conducted a retrospective review of medical records of all metastatic pancreatic cancer patients from 2010 to 2018 who received first line treatment with FFX or G+A at University of Arizona Cancer Center. Results: Thirty-five patients received combination treatment with G+A and 29 patients received FFX. Patient demographics: median age was 66 years in FFX vs 70 years in the G+A group; baseline CA-19-9 was 791 in FFX vs 738 in the G+A group. Median ECOG score was 1 for both groups. Median overall survival was 11.5 months in the FFX group (range 0-39 mos) vs 5 months in the G+A group (range 0-37 mos). Overall survival at 6 months was 75.9% vs 51.4% in FFX vs G+A groups respectively. Median progression-free survival was 6 months with FFX (range 0-25 mos) and 3 months with G+A (range 0-24 mos). Twenty-one of 29 patients in the FFX group pursued second line treatment, compared to 12 of 35 patients in the G+A group. Time to next treatment was 6 months in the FFX group vs 5 months in the G+A group. More adverse effects were noted with FFX, the most common being neuropathy and neutropenia, leading to treatment discontinuation due to adverse effects in 31% of patients, compared to 3% of patients in the G+A group. FFX patients required a higher median no. of office visits (35 visits vs 18 visits in the G+A group). Conclusions: FFX showed improved progression-free survival vs G+A; however, this could be due to more patients pursuing second line treatment in the FFX group. Compared to G+A, FFX patients had higher rates of treatment discontinuation due to adverse effects. FFX patients also required more office visits and further analysis is necessary to assess whether this resulted in poorer quality of life and increased total cost of care for patients treated with FFX.
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