Aim: We investigated the prognostic potential of pretherapy measurement of the neutrophil/lymphocyte ratio (NLR) in patients (n = 56) with non-small-cell lung cancer deemed suitable for treatment with nivolumab. Materials & methods: This was a multicenter, noninterventional, retrospective data analysis, involving five oncology centers. Results: Patients with prenivolumab NLR values of <5 and ≥5 had respective median overall survival (OS) values of 14.5 and 7.02 months (p = 0.0026). Patients with ≤2 and >2 metastatic sites had median OS values of 11.4 and 6.1 months, respectively (p = 0.0174). A Cox multiple regression model revealed baseline NLR ≥5 as the only variable significantly associated with decreased OS (p < 0.0447). Conclusion: Pretreatment elevated NLR values are associated with poor outcomes in patients with recurrent metastatic non-small-cell lung cancer treated with nivolumab.
Background: PDL1 expression in the tumor is used as a biomarker predictive of benefit from ICIs in NSCLC. We prospectively evaluated clinical, imaging and laboratory parameters to identify additional factors that could be used for patient (pt) selection. Methods: Pt and disease characteristics, sites (brain, liver, bones) and extent (1 vs ! 2) of metastases, concomitant use of steroids, antibiotics, or chronic use of proton pump inhibitors, neutrophil to lymphocyte ratio and LDH were prospectively collected from pts with NSCLC treated with ICIs in the 2 nd or 3 rd line. Response rate ( RR ), Progression free survival ( PFS ) and overall survival ( OS ) data were prospectively recorded. Results: Forty-four pts, median age 69 years, 50% squamous, 50% non-squamous, were included in the analysis. Performance status was 0-1 in 75% and 2 in 25% of pts, 92.7% were active/former smokers and PDL1 was !1% in 62% of pts with available PDL1 status. Partial response was recorded in 20% of pts, 30% had stable and 50% progressive disease. Median PFS and OS were 2.7 and 7.6 months, respectively. Prolonged (!14d, either within 30d pre-or during treatment) use of antibiotics (p ¼ 0,007) and concurrent steroids (p ¼ 0,047) were inversely correlated with response. In multivariate analysis, liver metastases [HR ¼ 4 (CI: 1,6 -9,9; p ¼ 0.003)], prolonged antibiotic use [HR ¼ 2,76 (CI: 1,8 -6,4; p ¼ 0,02)] and concurrent steroids [HR ¼ 3,3 (CI: 1,4 -8,1; p ¼ 0,009)] were independent predictors of shorter PFS, whereas, only antibiotics had a negative impact on OS [HR 4,6 ( CI: 1,[7][8][9][10][11][12] p ¼ 0,003 )]. Conclusions: To our knowledge this is the first prospective evaluation of routine clinical parameters potentially associated with outcome from ICIs in NSCLC. Our data are in accordance with previous retrospective reports regarding the adverse effect of antibiotics and steroids in the outcome of pts. Moreover, we show that in these pts liver metastases are predictive for inferior outcomes.
Background: Breast cancer is the most common cancer in Indian women. Triple negative breast cancer (TNBC) is associated with poor prognosis at any stage of diagnosis. It is an aggressive disease with a 5-year survival rate of 77% compared to 93% for other subtypes. Prevalence of TNBC in India is higher compared to western populations, making it an important target for early detection and treatment. Potential superiority of dose-dense chemotherapy in comparison with conventional regimen has been recently demonstrated in a meta-analysis in 2017 across various subsets of breast cancer. Aim of this study was to analyse survival outcomes in TNBC treated with dose dense chemotherapy at a tertiary care centre in India. Methods: Retrospective analysis of patients diagnosed with TNBC stage I-III in last 8 years treated with 2 weekly dose dense AC regimen (adriamycin at 60mg/m 2 and cyclophosphamide at 600mg/m 2 for 4 cycles followed by 2 weekly Paclitaxel at175 mg/m 2 for 4 cycles or weekly Paclitaxel at 80 mg/m 2 for 12 cycles) with growth factor support in adjuvant or neoadjuvant (NACT) setting. Locally advanced breast cancer (LABC) was defined as T > 5cm and N2 disease. Kaplan-Meier method and log rank test were used to estimate survival functions. Results: 97 patients with ER, PR and Her2neu receptor negative status were evaluated. Median age at diagnosis was 44 years (range 26 -68 years). 56.7% had stage II disease, 36% stage III and rest stage I (7.2%). Disease free survival (DFS) rate 6 SE at 2 years and 5 years was 90% 6 3% and 75% 6 5% respectively. Overall survival (OS) rate 6 SE at 5 years was 82% 6 6%. 24 patients received NACT out of which 12 (50%) patients had pathCR. The DFS rate did not differ significantly between adjuvant and neoadjuvant subgroups. Early breast cancer and LABC subgroups had a statistically significant difference in DFS rates (p ¼ 0.0002). Conclusions: To our knowledge, this is the first study in India to evaluate survival outcomes of dose dense therapy in TNBC. The improved DFS (75%) and OS (82%) in this high risk subgroup are very promising, especially in patients with early disease. We advocate use of dose dense regimen in all patients of TNBC in curative setting.
Background: Treatment with the checkpoint inhibitors ipilimumab (IPI) and nivolumab (NIVO) are associated with durable remissions in patients (pts) with solid tumors. We describe the durable remissions associated with these agents. There were 19 pts treated with IPI and 25 pts treated with NIVO and 1 pt was treated with a combination of IPI and NIVO. Methods: The purpose of this analysis is to describe the durable remissions associated with IPI and NIVO on a variety of solid tumors treated at a single centre. This is a retrospective data analysis from 45 pts treated either in an expanded access program, clinical trial setting or post-registration protocol. Results: A total of 45 pts (30 males, 15 females) were analyzed. Three pts with metastatic malignant melanoma (MMM), 18 with non-small cell lung cancer (NSCLC), 2 with renal cell carcinoma (RCC) and 2 with Hodgkin's disease (HD) were treated with NIVO and 19 with MMM received IPI. One NSCLC pt received a combination of IPI and NIVO (1 cycle). In total 167 cycles of NIVO (median ¼ 4, range 1-16), and 64 cycles of IPI (median ¼ 4 cycles, range 1-4) were administered. In the MMM group, there were 5 responses out 20 pts (25%) treated with IPI including 3 pts with durable complete response (CR) of 74þ, 46þ and 34þ months. One MMM pt treated with NIVO has an ongoing partial response (PR) of 23 months. Among the pts with NSCLC 6 responses were documented among the 18 pts treated with NIVO (33%). Two of these pts had very good and durable PRs of 10þ and 18þ months. One RCC pt treated with NIVO has an ongoing PR of 13þ months. Two heavily pretreated pts with HD treated with NIVO have very good PRs of 14þ and 13þ months. Additionally, a very PR was documented in the NSCLC pt treated with the combination IPI and NIVO. Conclusions: Anti-PD1 and anti-CTLA4 antibody treatment are associated with durable remissions in pts with a variety of solid tumours. Among our pts durable remissions and durable responses were documented in pretreated pts with RCC, NSCLC, HD and MMM.
Background: The presence of high levels of tumor infiltrating lymphocytes (TIL’s) has been associated with better prognosis in early triple-negative breast cancer (TNBC). The Immunoscore is a prognostic tool, which categorizes the densities of CD3 and CD8 cells in both invasive margins (IM) and the center of the tumor (CT) yielding a five-tiered classification (0-4). High immunoscores have been reported to predict improved outcomes in patients (pts) with colorectal cancer. Methods: The final retrospective report to be presented at the meeting will evaluate the immunoscore in 106 breast cancer (BC) patients undergoing neo-adjuvant chemotherapy. The current analysis include the results of the first 63 pts (TNBC=35, Luminal=20, Her2+=8) who received treatment with anthracycline and/or taxane and/or trastuzumab-based neo-adjuvant chemotherapy. Results: Pre-treatment tumor samples were immune-stained for T-cell (CD3, CD8) markers and quantitative analysis of the immune cells was carried out using a computer-assisted image analysis in different tumor locations. Results: A pathological complete response (pCR) was documented in 57%, 63% and 10% of TNBC, Her2-positive and luminal pts respectively. T-cell densities were significantly higher for TNBC pts compared to non-TNBC pts. A high density (more than 800mm2) of CD3 and CD8 positive T-cells in the CT was associated with higher pCR (CD8 CT: 69% vs. 16%, p = 0.00002) (CD3 CT: 57% vs. 14%, p=0.00015). Analysis of CD3 and CD8 in the IM (more than 500mm2) was also significant for an association with pCR (CD8 IM: 68% vs. 23%, p = 0.002) (CD3 IM: 68% vs. 16%, p=0.0005). In subgroup analyses, TNBC high density (more than 500mm2) of CD3 CT: 72% vs. 20%, p = 0.004 and CD8 CT: 78% vs. 35%, p = 0.001 was also significant for pCR. The immunoscore was also positively correlated with pCR (P=0.0002), and with clinical response (CR, PR, PD) (P=0.002). High immunoscore pts were at low risk of relapse, with 5-year TTR rates of 87.5 % (CI, 67-100 %) as compared to 54.9 % (CI, 29.6-100 %) in low immunoscore pts (HR=4.8 (CI 1.7-13.5), P<0.03). Conclusion: The results of this ongoing study show a significant prognostic and potentially predictive role for the immunoscore in BC pts, particularly in the TNBC subset. Citation Format: Bernardo Leon Rapoport, Simon Nayler, Jerome Galon, B Mlecnik, Teresa Smit, Jacqui Barnard-Tidy, Aurelie Fugon, Marine Martel, Ronwyn I Van Eeden, Ronald Anderson, Carol Benn. Focus on tumor infiltrating lymphocytes (TIL’s): High levels of spatially positioned CD3 and CD8 cells and high immunoscores are significantly associated with pathological complete responses in triple-negative breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-14.
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