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Introduction: The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. Methods: In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). Results: The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI+ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p=0.012) and DCR (82.8% vs. 53.4%, p=0.008). The median OS was 13.47 (95% CI: 7.79–19.15) months, and the six and 12- month survival rates were 71% and 52%. The median duration of response was 16.59months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06months (95% CI: 3.42– 6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). Conclusion: We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors. [ABSTRACT FROM AUTHOR]

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients. [ABSTRACT FROM AUTHOR]

This 5-year analysis of real-world data confirms the durable response and long-term survival with ICTs in a broader range of patients with metastatic urothelial carcinoma. After 24 months, PFS and OS curves remained nearly flat. The safety profile was consistent with previous reports, and no new safety signals were observed. Background: In this study, we report real-world results from the 5-year follow-up data of urothelial carcinoma patients treated with immune checkpoint blockade therapies (ICTs). Patients and Methods: Metastatic urothelial carcinoma patients treated with at least one course of ICT were included in the study. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of treatment with ICT, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. Results: Data of 201 eligible patients were analyzed. The median age of the patients was 66 (37-86) years, and 156 (84.3%) were male. The majority of patients (94.6%) had Eastern Cooperative Oncology Group (ECOG) PS scores of 0 to 1 and primary tumor in the bladder was predominant (87.5%). The median follow-up time was 54 (1.15-65) months. The rate of complete response (CR) to ICT, partial response (PR) rate, and ORR were 10.4% (n = 21), 22.4% (n = 45), and 32.4% (n = 66), respectively. The median duration of response (DOR) was 34.8 months (95% confidence interval [CI], 29.2-42.1). Of the 66 patients who responded to treatment, 28 (42%) had an ongoing response at the time of the analysis. Median PFS and OS were 3.8 (2.6-5.8) months and 9.4 (7.4-11.4) months, respectively. The 5-year PFS and OS rates were 9.8% and 12.8%, respectively. Fifty-eight percent of patients experienced a treatment-related adverse event of any grade, and 33 (16.4%) patients had a grade 3 to 4 adverse event. Conclusion: This 5-year analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients. [ABSTRACT FROM AUTHOR]

To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time. [ABSTRACT FROM AUTHOR]

Objectives: Advanced stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients.Methods: A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed.Results: At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51-6.82), and the median overall-survival (OS) time was 16.8 months (95% CI: 13.9-19.6). Treatment choice (p < 0.001 HR:0.70 CI95% 0.55-0.9), performance status (p < 0.001 HR:2.74 CI 95% 2.12-3.54) and neutrophil-to-lymphocyte ratio (NLR) (p = 0.02 HR:1.38 CI 95% 1.03-1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p < 0.001 HR:1.78 CI 95% 1.5-2.3), Systemic Immune-inflammation Index (SII) (p < 0.001 HR:0.51 CI95% 0.36-0.73) and stage at diagnosis (p = 0.002 HR:1.79 CI 95% 1.24-2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC (p < 0.001 HR:0.55 CI 95% 0.38-0.79; p = 0.007 HR:0.51 CI95% 0.31-0.83, respectively).Conclusion: SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions. [ABSTRACT FROM AUTHOR]

• HL is one of the rare curable entities in adults with 80% long term survival chance and risk scoring before planning the management of the patients is very important. • There is significant improvement both in diagnostic imaging modalities including PET/CT and also treatments including targeted and immunotherapeutic approaches for this unique entity. • Despite these significant improvement in outcomes, 20% of the patients have refractory disease or show relapse. • Clinicians need an ideal scoring system to identify the risk of every patient and the most commonly used clinical scoring system for a long time for this aim in cHL is IPS-7 and this scoring system has been replaced by IPS-3 system. • Here it has been reported IPS-3 scoring system has been evaluated and validated in 1012 cases. The aim of this study is to validate the IPS-3 scoring system as a prognostic indicator in 1012 patients with advanced stage classical Hodgkin Lymphoma (cHL) treated by doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD). According to the IPS-3 scoring system only 3.5 % had high risk and 50.8 % had low risk disease disease and 45.8 % of the cases had intermediate risk disease. Each factors of IPS-7 and IPS-3 scoring systems (age, sex, stage hemoglobin, albumin, lymphocyte count and white cell count) were found to be significant for overall survival (OS) and progression free survival (PFS) according to univariate analyses. Two different multivariate Cox analyses were performed for OS and PFS including the IPS-3/ IPS-7 scoring system parameters. Among 7 risk factors of IPS scoring system, gender and albumin were not found as independent risk factors for both OS and PFS according to cox regression model. But all parameters such as age, stage and hemoglobin those included in IPS-3, were found to be independent significant risk factors for both models obtained for OS and PFS. The results of the study shows that the IPS-3 scoring system can be used as a prognostic indicator in ABVD treated patients in every day practice which is more easily calculate according to the IPS-7. [ABSTRACT FROM AUTHOR]