Hyperprogressive disease (HPD) in head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint inhibitors (ICI).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6029-6029 ◽  
Author(s):  
Salvatore Alfieri ◽  
Roberto Ferrara ◽  
Giuseppina Calareso ◽  
Stefano Cavalieri ◽  
Francesca Platini ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Subsequent Treatment ◽  
Smoking History ◽  
Rank Test ◽  
Neutrophil Lymphocyte Ratio ◽  
Kaplan Meier ◽  
Hyperprogressive Disease ◽  
Definition Of ◽  
Ecog Ps

6029 Background: HPD was described in 9% of cancer patients (pts) treated in phase I trials, in 13.8% of advanced non-small cell lung cancer and 29% of 34 HNSCC pts upon ICI. A better definition of the hallmarks and survival outcomes of HPD pts in a larger cohort of HNSCC is still lacking. Methods: We retrospectively analyzed all advanced HNSCC pts treated with ICI at our Institution between October 2014 and December 2018. Three scans, performed before ICI, at baseline and at first evaluation during ICI, were assessed according to RECIST 1.1. Tumor Growth Kinetics (TGK) pre- (TGKpre) and post-baseline (TGKpost) were measured as previously reported (Saâda-Bouzid E, Ann Oncol 2017). Pts were defined HPD if they had progression at first radiological evaluation and TGKpost/TGKpre ≥2. Correlation between HPD and clinical characteristics was performed by Fisher or t-student test. Median overall survival (mOS) and progression free survival (mPFS) were estimated using the Kaplan-Meier method and compared between HPD and non-HPD using the log-rank test. Results: Ninety pts were eligible: 18% were female, 4% had ECOG PS ≥ 2, 73% smoking history, 37% oropharyngeal cancer (61% HPV+), 65% locoregional disease (89% previously irradiated), 54% received combined immunotherapy, 75% in ≥ 2nd line. Two out of 90 pts had TGKpre = 0 and were not evaluable for TGK ratio. HPD was observed in 7.9% (7/88) of pts. HPD pts were significantly younger compared to non-HPD pts (median age 53 ± 3.7 vs 63.3 ± 0.9 years, p = 0.002) and had a significantly higher median neutrophil-lymphocyte ratio (NLR) (11.5 ± 3.5 vs 6.4 ± 0.4, p = 0.004). Overall, mOS and mPFS were 7.5 (95% CI: 4.2-10.8) and 2.2 months (95% CI: 0.9-3.4), respectively. At a median follow-up of 20.9 months (95% CI: 19-22.8), HPD pts had a significantly worse mPFS compared to non-HPD pts [1.8 (95% CI: 1.5-2.2) vs 3.5 (95% CI: 2.2-4.8) months; p = 0.001]. HPD correlated with a not significant trend in lower mOS compared to non-HPD group [3.7 (95% CI: 2.4-5.1) vs 8.3 (95% CI: 4.1-12.5) months; p = 0.348]. Three (43%) out of 7 HPD pts early switched to chemotherapy after PD to ICI having a mOS of 8.1 months (range 3.7-25.3). Excluding these 3 pts, HPD correlated with a significantly worse mOS compared to non-HPD [2.6 (95% CI: 1.9-3.3) vs 8.3 (95% CI: 4.1-12.5) months; p = 0.006]. Conclusions: HPD was identified in 7.9% of HNSCC and correlated with younger age and higher NLR. HPD pts who did not receive a subsequent treatment had poorer mPFS and mOS. The assessment of HPD in a control cohort of advanced HNSCC upon standard chemotherapy is ongoing.

Evaluation of different MET genotypes as biomarkers for immunotherapy outcomes in NSCLC patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21032-e21032
Author(s):  
Xuanzong Li ◽  
Linlin Wang
Keyword(s):  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Rank Test ◽  
Wild Type ◽  
Exact Test ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Tumor Mutational Burden ◽  
The Difference ◽  
Nsclc Patients

e21032 Background: Previous studies suggested that MET exon 14 ( METex14) mutation regarding as a distinct subset was sensitive to MET-inhibitors, but poorly response to immunotherapy. Conversly, MET non-exon-14 (non-ex14) mutations including those undetermined functions and affecting the kinase or extracellular domains were found to be associated with the resistance to MET-inhibitors. However, therapeutic strategies for MET-non-ex14 mutant cancer are still largely unknown, and the relationship between MET-non-ex14 mutations and the efficacy of immune checkpoint inhibitors (ICIs) has never been reported. Using two public ICIs-treated cohorts, we aimed to assess the role of MET mutations including both METex14 and MET-non-ex14 mutations in NSCLC patients undergoing ICIs therapy. Methods: A total of 385 ICIs-treated NSCLC patients were enrolled to our study. MET mutations were defined as any nonsynonymous mutations, and we divided them into METex14 and MET-non-ex14 mutation subsets according to the mutated-position on MET. Kruskal-Wallis test was used to analyze the difference of tumor mutational burden (TMB) score, and the Fisher’s exact test was applied to compare the rates of durable clinical benefit (DCB). Log-rank test was used to analyze the differences between Kaplan-Meier survival curves. Results: In the entire cohort, we found that 17 patients (17/385, 4.4%) had MET mutations, most of which were pure METex14 mutations (10/17, 58.8%). The median TMB of patients in the entire NSCLC cohort was 6.89 mut/Mb. MET-non-ex14 mutant patients (7/385, 1.8%) possessed a significantly higher TMB than METex14-mutant (10/385, 2.6%) and MET wild-type (368/385, 95.6%) sub-cohorts, respectively (median TMB, 17.92 mut/Mb versus 4.17 mut/Mb, p = 0.008; 17.92 mut/Mb versus 6.96 mut/Mb, p = 0.01, respectively). DCB was more common in patients harbored MET-non-ex14 mutations than patients with METex14 mutations and MET wild-type (66.7% versus 14.3%, p = 0.103; 66.7% versus 29.9%, p = 0.075, respectively). We found that patients with MET-non-ex14 mutations had a numerically longer progression free survival (PFS) than those with METex14 mutations and MET wild-type (p = 0.169). Moreover, the PFS was significantly longer in MET-non-ex14-mutant subgroup than patients with METex14 mutations (median PFS, 9.1 versus 2.1 months, p = 0.025). Correspondingly, the overall survival (OS) was significantly longer in MET-non-ex14-mutant subgroup than their wild-type counterparts (median OS, not reached versus 11 months, p = 0.039). Additionally, patients with MET-non-ex14 mutations exhibited relatively better OS versus METex14-mutant patients (median OS, not reached versus 18 months, p = 0.175). Conclusions: MET-non-ex14 mutations were associated with higher TMB, improved DCB rate, and could act as a favorable prognostic biomarker in ICIs-treated NSCLC patients.

High baseline lymphocyte count is a predictive biomarker of prolonged time to progression in patients with advanced solid tumors receiving checkpoint inhibitors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14532-e14532
Author(s):  
Mariangela Maltese ◽  
Stefano Panni ◽  
Silvia Lazzarelli ◽  
Matteo Brighenti ◽  
Federica Negri ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Lymphocyte Count ◽  
Checkpoint Inhibitors ◽  
Absolute Lymphocyte Count ◽  
Predictive Biomarker ◽  
Rank Test ◽  
Advanced Solid Tumors ◽  
Time To Progression ◽  
Neutrophil Lymphocyte Ratio ◽  
Kaplan Meier

e14532 Background: Biomarkers predicting response to checkpoint inhibitor are needed to better select patients most likely to benefit from treatment. We observed that baseline absolute lymphocyte count (ALC) can predict durable responses to anti-PD-1 antibodies in various malignancies. Methods: This is a retrospective analysis of patients with advanced solid tumors treated with anti-PD-1 antibodies. Pembrolizumab was given at 2 mg/kg every 3 weeks, Nivolumab at 3 mg/kg every 2 weeks. Peripheral ALC and absolute neutrophil count (ANC) from routine safety labs were collected at baseline, cycle 4 and cycle 8. Evaluation of response was based on irRECIST. Neutrophil lymphocyte ratio [NLR = ANC/ALC] was stratified by ≤4 or > 4. The lymphocyte count cutoff was 1000/mm3. Time to progression (TTP) and overall survival (OS) were estimated with the Kaplan-Meier method. Differences between groups were estimated with the log rank test. Results: We have retrospectively evaluated 40 patients with unresectable stage III/IV Non Small Cell Lung Cancer (squamous n. 17; 42.5%, adenocarcinoma n. 7; 17.5%), Malignant Melanoma (n.11; 27.5%), Renal Cell Carcinoma (n.5; 12.5%) treated with anti-PD-1 antibodies. 6 pts (15%) received treatment as 1st line, 14 pts (35%) as 2nd line, 20 pts (15%) as ≥ 3rd line. We observed a 29% partial response (PR), 31% stable disease (SD) and 40% progressive disease (PD). The overall response rate (ORR) was 29% [I.C. 95% 13-42]. Median TTP was 5.5 months [IC 95% 3.3-NR]. Median OS was not reached. Pts with baseline ALC ≥1000/mm3 had significantly longer TTP (median value not reached), compared with those who had ALC < 1000/mm3 (median TTP 2.8 months), p = 0.01. There was also a trend for longer TTP in patients with NLR < 4 vs ≥4 (4.9 vs 10.5 months, p 0.44). Conclusions: In our observation baseline ALC ≥1000/mm3 is a predictive biomarker of prolonged TTP in patients treated with anti-PD-1 antibodies. The potential predictive value of this test should be prospectively validated.

Impact of previous nephrectomy on clinical outcome of metastatic renal carcinoma treated with immune-oncology (I-O):A real-world study on behalf of Meet-URO group (MeetUro-7b).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17088-e17088
Author(s):  
Marco Stellato ◽  
Daniele Santini ◽  
Ugo De Giorgi ◽  
Elena Verzoni ◽  
Chiara Casadei ◽  
...  
Keyword(s):  
Real World ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Rank Test ◽  
Prognostic Impact ◽  
Curative Intent ◽  
Kaplan Meier ◽  
The Difference ◽  
Third Line ◽  
Ecog Ps

e17088 Background: Immuno-oncology (IO) treatment demonstrated to improve Overall Survival (OS) in metastatic renal cell carcinoma (mRCC). The prognostic impact of previous citoreductive nephrectomy (CN) and radical nephrectomy with curative intent in patients (pts) treated with IO is not well defined. Methods: 229 eligible pts, with a least one radiological assessment of response according to the RECIST 1:1 criteria, were retrospectively collected from 16 Italian referral centers. Baseline characteristics, outcome data including progression-free survival (PFS) and OS were collected. Kaplan-Meier method and log-rank test were performed to compare PFS and OS between groups. Results: 153(66.8%) pts received IO as second line, 61(26.6%) as third line and 15(6.6%) pts as further line. 54 pts (23.6%) were good risk, 144(62.9%) were intermediate and 31(13.5%) were poor risk according to IMDC score. 189(82.5%) pts underwent nephrectomy (of them 72(32.4%) pts had synchronous metastatic disease and underwent CN), while 40(17.4%) pts did not. Nephrectomy was performed before IO treatment. ECOG PS, at the beginning of IO, was 0 for 167 pts (72.9%), the other 62 (27.1%) had ECOG PS 1 or 2. At a median follow up time of 17.5 months (mo), 13 (5.7%) pts are still in treatment while 216 (94.3%) experienced progression. 81 (35.3%) pts were treated after IO progression with mTOR and VEGFR inhibitors. 63 (27.5%) pts continued IO beyond progression. G3-G4 iAE were reported in 46 pts (20%). Median IO-PFS was 4.5 months in pts who did not undergo nephrectomy and 2.9 mo in pts who did (HR log rank 0.713, 95%CI 0.4788 to 1.063; p= 0.0582). Median IO-OS was 18.4 mo in pts who underwent nephrectomy and 10.3 mo in pts who did not (HR log rank 1.915, 95%CI 1.118 to 3.281; p= 0.0024). The difference in OS was irrespective of the IMDC criteria and the lines of treatment. Conclusions: In our real world experience, in mRCC pts treated with IO, previous nephrectomy was associated with a better outcome in terms of OS with all the limitations of a retrospective collection.

A phase II study of pembrolizumab in combination with palliative radiotherapy (RT) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1047-1047 ◽  
Author(s):  
Romualdo Barroso-Sousa ◽  
Ian E. Krop ◽  
Lorenzo Trippa ◽  
Zhenying Tan-Wasielewski ◽  
Tianyu Li ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Metastatic Breast ◽  
Palliative Radiotherapy ◽  
Progression Free Survival ◽  
Optimal Method ◽  
Neutrophil Lymphocyte Ratio ◽  
Ecog Ps

1047 Background: RT is frequently used for palliation in MBC. In animal models its use has been reported to induce distant (abscopal) tumor responses when combined with immune checkpoint inhibitors. Here, we report the safety and efficacy of palliative RT plus pembrolizumab in a phase II single-arm study in patients (pts) with HR+/HER2- MBC. Methods: Eligible pts had HR+/HER2- MBC, ECOG PS <2, indication for palliative RT, and ≥1 measurable lesion outside of the RT field; there was no limit on prior lines of therapy. A total RT dose of 20 Gray was delivered over 5 daily fractions. Pembrolizumab was given at 200 mg IV 2-7 days before day 1 of RT, then every 3 weeks until disease progression. The primary endpoint was objective response rate (ORR) outside the field of radiation by RECIST v1.1. Using the Simons “optimal” method, if ≥ 1/8 pts responded during the first stage, 19 more would be enrolled. If ≥ 3/27 responded, the null hypothesis (ORR=3%) would be rejected in favor of a 20% ORR. Predefined secondary endpoints included progression free survival (PFS) and toxicity. Analyses associating PD-L1 expression, tumor-infiltrating lymphocytes (TIL), and neutrophil/lymphocyte ratio (NLR) with outcomes were exploratory. Results: Eight women were enrolled into the first stage of the trial; no objective responses were seen, and the study was closed to further accrual. The median age was 59y (37-68y), 6 (75%) had ECOG PS 1, all had bone and 5 (63%) had liver metastases. The median number of prior cytotoxic therapies for MBC was 2 (range 0 to 8). While one patient had a PR by RECIST criteria, this patient experienced concurrent clinical progression. Two pts had SD < 16 weeks and 5 had PD as best response. The median PFS was 1.4 months (95% CI 0.4 – 2.1). All-cause adverse events occurred in 87.5% of pts (G3-4, 12.5%). TIL were available for 6 pts: 4 had ≤10%, and 2 > 10%. Among 5 pts with PD-L1 status available, 2 were positive. Six pts had NLR > 4. Conclusions: Pembrolizumab combined with RT was well-tolerated, and no unexpected adverse events were observed; however, clinical benefit of the combination was not demonstrated in this heavily pretreated HR+ population. Clinical trial information: NCT03051672.

scholarly journals PD-L1 expression is a promising predictor of survival in patients with advanced lung adenocarcinoma undergoing pemetrexed maintenance therapy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Qin ◽  
Lili Jiang ◽  
Min Yu ◽  
Yanying Li ◽  
Xiaojuan Zhou ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
Bivariate Correlation ◽  
Kaplan Meier ◽  
Alk Positive ◽  
Ecog Ps

Abstract This study aimed to identify potential predictive factors for the survival of advanced lung adenocarcinoma patients undergoing pemetrexed maintenance therapy. 122 advanced lung adenocarcinoma patients who received pemetrexed maintenance therapy were retrospectively analyzed. Kaplan–Meier method with Log-rank test was used for survival analysis. Univariate and multivariate Cox regression were performed to evaluate prognostic factors for overall survival (OS) and progression-free survival (PFS). Bivariate correlation analysis was used for exploratory purpose. For the whole cohort of 122 patients, median PFS was 11.97 months (95% CI 10.611–13.329) and estimated median OS was 45.07 months (95% CI 31.690–58.450). The mPFS of ALK-positive patients was superior to negative patients (18.27 vs. 11.90 months; P  = 0.039). Patients with ECOG PS 0 (14.4 vs. 11.1 months; p = 0.040) and patients with single-organ metastasis (19.0 vs. 11.0 months; p = 0.014) had prolonged median PFS. Compared with the low PD-L1 expression group, PFS of high PD-L1 expression group were improved (13.6 vs. 11.1 months, p = 0.104, at 1% cut-off; 17.5 vs. 11.1 months, p = 0.009, at 10% cut-off; and 27.5 vs. 11.4 months, p = 0.005, at 50% cut-off). No differences were found between EGFR positive and negative patients. PD-L1 expression was an independent prognostic factor for both PFS and OS times (PFS: HR, 0.175; P  = 0.001; OS: HR, 0.107; P  = 0.036). Bivariate correlation showed a significant positive correlation between PD-L1 expression and PFS (correlation coefficient R = 0.485, P  < 0.001). High PD-L1 expression could be a potential effective predictor for favorable survival of advanced lung adenocarcinoma patients undergoing pemetrexed maintenance therapy.

Atezolizumab (atezo) and subsequent therapies in patients (Pts) with metastatic urothelial carcinoma (mUC) outside clinical trials.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 432-432
Author(s):  
Pedro C. Barata ◽  
Vadim S. Koshkin ◽  
Prateek Mendiratta ◽  
Dharmesh Gopalakrishnan ◽  
Matt Karafa ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Subsequent Treatment ◽  
Entire Cohort ◽  
Prior Therapy ◽  
Best Response ◽  
Prior Surgery ◽  
Never Smokers ◽  
Ecog Ps

432 Background: The use of immune checkpoint inhibitors (ICI) has revolutionized treatment of mUC. Little is known about the outcomes and safety profile of pts treated with ICI outside of clinical trials, as well as about responses to subsequent therapies. Methods: A retrospective analysis of consecutive mUC pts who received ≥1 dose of atezo 1200 mg every 3 weeks from May 2016 through April 2017 was conducted. Exploratory assessments included overall response rate according to RECIST v1.1, progression-free survival (PFS) and overall survival (OS) since time of treatment initiation, and treatment-related adverse events (TRAE) according to CTCAE v4.03. Results: A total of 79 pts were identified; median age 72 (29-93), 71% men, 27% never smokers, 66% pure urothelial histology, 49% visceral disease, 76% ECOG PS 0-1 and 61% with 1-2 Bellmunt risk factors. Most pts (79%) had primary tumor in bladder, 62% prior surgery and 75% ≥ 1 prior treatment. Most pts (71%) had 1-2 prior lines of treatment, 4% of pts had 3 lines, and 25% of pts had no prior systemic treatment. Pts received a median of 4 atezo doses (1-18) and median treatment duration was 3.2 months (95%CI 1.9-4.5). In 55 pts evaluable for response, 25% had partial response, 36% stable disease and 38% progressive disease, with a median time to best response of 2.7 months (1.3-7.4) and median PFS 4.5 months (95%CI 3.4-5.6). Estimated OS for the entire cohort was 8.3 months (median not reached) and was not significantly different based on prior therapy. TRAE of any grade were noted in 89% of pts and mostly included fatigue (63%) and anorexia (28%). Two pts had grade 4 hyperbilirubinemia, and no toxic deaths were noted. At time of data analysis, 34% of pts remained on atezo, 16% received 1-2 subsequent treatments with median duration of 1.3 months ( 95%CI 0.5-2.2) and 8% PR as best response, 41% were referred to hospice or died, and 9% were lost to follow-up. Conclusions: Pts with mUC treated with atezo had comparable outcomes and toxicity to those reported in clinical trials. Pts who progressed on atezo were unlikely to receive subsequent treatment and the benefit of such treatment was limited. Results may impact clinical trial designs and timing in regard to ICI.

Three-year overall survival update from the PACIFIC trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8526-8526 ◽  
Author(s):  
Jhanelle Elaine Gray ◽  
Augusto E. Villegas ◽  
Davey B. Daniel ◽  
David Vicente ◽  
Shuji Murakami ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Smoking History ◽  
Rank Test ◽  
Kaplan Meier ◽  
Primary Endpoints ◽  
The Pacific ◽  
Patient Reported

8526 Background: In the phase 3 PACIFIC study of patients with unresectable, Stage III NSCLC without progression after chemoradiotherapy (CRT), durvalumab demonstrated significant improvements versus placebo in the primary endpoints of progression-free survival (HR, 0.52; 95% CI, 0.42–65; P < 0.0001) and overall survival (OS; HR, 0.68; 95% CI, 0.53–0.87; P = 0.00251). Safety was similar and durvalumab had no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study. Methods: Patients with WHO PS 0/1 (any tumor PD-L1 status) who received ≥2 cycles of platinum-based CRT were randomized (2:1), 1–42 days following CRT, to receive durvalumab 10 mg/kg intravenously every 2 weeks or placebo, up to 12 months, and stratified by age, sex, and smoking history. OS was analyzed using a stratified log-rank test in the ITT population. Medians and OS rates at 12, 24 and 36 months were estimated by Kaplan-Meier method. Results: In total, 713 patients were randomized of whom 709 received treatment (durvalumab, n = 473; placebo, n = 236). The last patient had completed the protocol-defined 12 months of study treatment in May 2017. As of January 31, 2019 (data cutoff), 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months (range, 0.2–51.3). Updated OS remained consistent with that previously reported (stratified HR 0.69, 95% CI, 0.55–0.86), with the median not reached (NR; 95% CI, 38.4 months–NR) with durvalumab versus 29.1 months (95% CI, 22.1–35.1) with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. After discontinuation, 43.3% and 57.8% in the durvalumab and placebo groups, respectively, received subsequent anticancer therapy (9.7% and 26.6% subsequently received immunotherapy). OS subgroup results will be presented. Conclusions: Updated OS data from PACIFIC, including 3-year survival rates, underscore the long-term clinical benefit with durvalumab following CRT and further establish the PACIFIC regimen as the standard of care in this population. Clinical trial information: NCT02125461.

Comparative efficacy of sorafenib dose in patients with advanced hepatocellular carcinoma (HCC) with varying liver dysfunction.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 369-369
Author(s):  
Sukeshi R. Patel ◽  
Raed Moh'd Taiseer Al-Rajabi ◽  
Norma Ketchum ◽  
Ting-Wei Lu ◽  
Brad H. Pollock ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
South Texas ◽  
Rank Test ◽  
Advanced Hepatocellular Carcinoma ◽  
Vein Thrombosis ◽  
Kaplan Meier ◽  
Dose Modifications ◽  
Ecog Ps

369 Background: Sorafenib (SOR) is the only FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). In clinical practice, there are limited efficacy data related to dose modifications, which are often required. Given the high prevalence of HCC in South Texas, we assessed the efficacy and safety of SOR therapy in relation to dose and Child Pugh score (CP). Methods: Retrospective analysis of HCC patients (pts) receiving SOR from 2008-2013. Median progression-free survival (mPFS) and median overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). A proportional hazards regression model was used to assess the significance of SOR (low, high) by CP (A, B) interaction. Results: 107 pts were included. Median age 57 (41-93). Males 83%. Hispanic 72%, White 24%. ECOG PS 0–1 93%. Causes of cirrhosis: Hepatitis C 67%, Hepatitis B 5%, EtOH 60%. Portal vein thrombosis 33%, extrahepatic disease 39%. CP (available for 106 pts): A 57%, B 43%. mOS was 10.2 months (mo) (95% CI: 7.8-13.5); mPFS was 5.2 mo (95% Cl: 3.8-7.2). In subgroup analysis, mOS for 800 mg/day was 12.8 mo vs 6.6 mo for 400 mg/day (HR 0.59, p=0.04). mPFS for 800 mg/day was 5.9 mo vs 3.5 mo for 400 mg/day (HR 0.66, p=0.07). In CP A pts, higher SOR dose did not improve survival; however, in CP B pts, there were statistically significant improvements in mPFS and mOS (Table). The effect of dosage varied significantly with CP category (A, B) for both OS (p=0.002) and PFS (p=0.03). Conclusions: Historically, CP B advanced HCC pts have worse survival and tolerability to higher doses of SOR when compared to CP A. Our study suggests CP B pts should be considered for SOR 800 mg/day to improve survival with optimal management of toxicity but warrants further prospective studies. [Table: see text]

Neutrophil lymphocyte ratio (NLR) as a clinical biomarker predictive of outcomes with immune checkpoint inhibitor therapy in genitourinary cancers.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 453-453 ◽  
Author(s):  
Ghayathri Jeyakumar ◽  
Naresh Bumma ◽  
SeongHo Kim ◽  
Craig Landry ◽  
Heejin Kim ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Smoking Status ◽  
Prognostic Score ◽  
Unmet Need ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Rank Test ◽  
Neutrophil Lymphocyte Ratio ◽  
Genitourinary Cancers

453 Background: Immune checkpoint inhibitors (ICI) have been approved in genitourinary cancers (GU) such as renal cell carcinoma (RCC) and urothelial carcinoma (UC). There is an unmet need to determine factors predictive of response, to guide therapeutic selection in these cancers. We evaluated NLR as a predictor of response, progression free survival (PFS), and overall survival (OS) in patients treated with ICI. Other known prognostic clinical factors assessed were age, race, and smoking status and for RCC the prognostic score per MSKCC (Memorial Sloan Kettering) and Heng criteria. Methods: Regulatory approval was obtained. A retrospective chart review of RCC and URC patients at Karmanos Cancer Institute, treated with ICI based therapy was conducted. Data was collected on demographics, smoking status, prognostic scoring, NLR pretherapy, and post 4 doses of ICI. Correlation with clinical PFS and OS was conducted by univariable and multivariable analyses. Log-rank test was used to compare PFS and OS. Results: 57 pts were evaluated with median age 62 yrs (range, 24-85). 11 (19%) were African American (AA) and 31 (54%) were smokers. Pretherapy NLR<4 and ≥4 was seen in 38 (67%) and 19 (33%) pts respectively. 13 (31%) RCC pts were treated with > 1 VEGF therapy and 24(57%) pt were treated for > 6 mths and 14/15 UC pts were pretreated. RCC pts treated with > 6 mths and > 12 mths of VEGF therapy had a shorter PFS (HR =2.31, p= 0.028; HR = 2.075, p= 0.051 respectively). AA had shorter PFS and OS with ICI in RCC but not in UC (HR=3.72, p=0.001; HR= 40.8; p=0.001; HR=0.49, p=0.5; HR=0.85, p=0.88, respectively). Conclusions: Pretherapy NLR ≥4 was a statistically significant predictor of shorter PFS and OS with ICI therapy in RCC. NLR is an easily applicable clinical predictive factor that can help guide therapy, after validation of these findings in a larger population dataset. [Table: see text]

637 Immune-related adverse events (irAEs) may indicate a favorable prognosis in metastatic renal cell carcinoma (mRCC) patients treated with immune checkpoint inhibitors (ICI)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A672-A673
Author(s):  
Dylan Martini ◽  
Sean Evans ◽  
Subir Goyal ◽  
Yuan Liu ◽  
T Anders Olsen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Emory University

BackgroundImmune checkpoint inhibitors (ICI) have become an increasingly utilized treatment in metastatic renal cell carcinoma (mRCC). Although they have a favorable toxicity profile, immune-related adverse events (irAEs) can have a significant impact on patients‘ quality of life. It is not well understood whether irAEs are associated with improved clinical outcomes. We investigated the relationship between irAEs and clinical outcomes in mRCC patients treated with ICI.MethodsWe performed a retrospective study of 200 patients with mRCC who received ICI at Winship Cancer Institute of Emory University from 2015–2020. Clinical outcomes were measured by overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). OS and PFS were calculated from ICI-initiation to date of death and radiographic or clinical progression, respectively. CB was defined as a best radiographic response of complete response (CR), partial response (PR), or stable disease (SD) for >6 months per response evaluation criteria in solid tumors (RECIST) version 1.1. Toxicity data was collected from clinic notes and laboratory values. The association with OS and PFS was modeled by Cox proportional hazards model. Kaplan-Meier curves were created for survival estimates.ResultsMost patients were males (71%), and 78% had clear-cell RCC (ccRCC). Most patients (58%) received anti-PD-1 monotherapy. The majority were international mRCC database consortium (IMDC) intermediate (57%) or poor-risk (26%). Anti-PD-1 monotherapy was the most common (58%) treatment regimen and most patients received ICI as first (38%) or second-line (42%) treatment. One-third of patients (33%) experienced an irAE, with the most common being endocrine (13%), gastrointestinal (11%), and dermatologic (10%). Patients who experienced irAEs had significantly longer OS (HR: 0.52, 95% CI: 0.32–0.87, p=0.013), higher chance of CB (OR: 2.10, 95% CI: 1.11–4.00, p=0.023) and showed a trend towards longer PFS (HR: 0.71, 95% CI: 0.49–1.02, p=0.065) in MVA (table 1). Patients who had thyroid irAEs had significantly longer OS, PFS, and higher chance of CB in MVA (table 1). The objective response rate was higher for patients who experienced irAEs (34% vs. 18%). Patients who experienced irAEs had significantly longer median OS (44.5 vs. 18.2 months, p=0.005) and PFS (7.5 vs 3.6 months, p=0.0028) compared to patients who did not (figure 1).Abstract 637 Table 1MVA* of association between irAEs and clinical outcomesAbstract 637 Figure 1Kaplan-Meier curves of association between immune-related adverse events (irAEs) and overall survival (OS, top panel) and progression-free survival (PFS, bottom panel)ConclusionsWe showed that mRCC patients who experienced irAEs, particularly thyroid irAEs, had improved clinical outcomes. This suggests that irAEs may be prognostic of favorable outcomes in mRCC patients treated with ICI. Larger, prospective studies are needed to validate these findings.AcknowledgementsResearch reported in this publication was supported in part by the Breen Foundation and the Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Trial RegistrationNot applicableEthics ApprovalThis retrospective study was approved by the Emory University Institutional Review Board.ConsentNot applicableReferencesNot applicable

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