scholarly journals Association of programmed death ligand 1 expression with prognosis among patients with ten uncommon advanced cancers

2020 ◽  
Vol 6 (8) ◽  
pp. FSO616
Author(s):  
Torben Steiniche ◽  
Morten Ladekarl ◽  
Jeanette Bæhr Georgsen ◽  
Simon Andreasen ◽  
Michael Busch-Sørensen ◽  
...  

Aim: PD-L1 expression and high levels of microsatellite instability (MSI-H) may predict response to checkpoint inhibitors, but their prevalence and prognostic value are unknown in many cancers. Methods: We retrospectively evaluated PD-L1 combined positive score (CPS) and MSI-H and their association with clinical outcomes among patients with ten advanced uncommon cancers. Results: 398 of 426 patients (93%) had a valid PD-L1 result; most (242; 61%) had CPS ≥1. Prevalence of MSI-H tumors was 8/360. Median overall survival was shorter among patients with PD-L1 CPS ≥1 tumors after first-line treatment (23.0 vs 39.7 months, p = 0.014). Conclusion: PD-L1 was commonly expressed in solid tumors, and CPS ≥1 was associated with shorter overall survival. Prevalence of MSI-H was low.

2021 ◽  
Vol 64 (5) ◽  
pp. 342-348
Author(s):  
Jin Won Kim

Immuno-oncological treatment approaches, particularly with the use of immune checkpoint inhibitors such as antiprogrammed death 1 (PD-1)/programmed death ligand 1 antibody or anti-cytotoxic T-lymphocyte associated protein 4 antibody, have become the standard treatment for gastrointestinal cancers. However, gastrointestinal cancers show an overall modest tumor response to immune checkpoint inhibitors. Nevertheless, subgroups such as tumors that are DNA mismatch repair-deficient or have high microsatellite instability particularly benefit from immune checkpoint inhibitors. Even in the first-line setting for colorectal cancer, the clinical efficacy of pembrolizumab, an anti–PD-1 antibody, was superior to that of chemotherapy. Recently, a combination of atezolizumab, an anti-programmed death ligand 1 antibody, and bevacizumab was approved as the first-line treatment for hepatocellular carcinoma, and was reported as superior to sorafenib. Nivolumab, an anti–PD-1 antibody that is added to chemotherapy as the first-line treatment for gastric cancer, resulted in longer survival compared with chemotherapy alone. Further studies are ongoing to investigate additional immune checkpoint inhibitors for other gastrointestinal cancers. This review aims to provide an overview of the results of clinical trials for immune checkpoint inhibitors in gastrointestinal cancers, including colorectal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and biliary tract cancer.


Author(s):  
Ashley L. Monsrud ◽  
Vaidehi Avadhani ◽  
Marina B. Mosunjac ◽  
Lisa Flowers ◽  
Uma Krishnamurti

Context.— Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in invasive anal squamous cell carcinoma (ASCC). Objective.— To assess PD-L1 expression in patients with ASCC and correlate it with clinicopathologic factors and clinical outcomes. Design.— Fifty-one cases of ASCC were immunostained for PD-L1. PD-L1 expression by combined positive score and tumor proportion score was correlated with age, gender, HIV status, HIV viral load, CD4 count, stage, and outcomes. Kaplan-Meier curves for overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P < .05 was considered statistically significant). Results.— PD-L1 was positive in 24 of 51 cases (47%) by combined positive score and in 18 of 51 (35%) by tumor proportion score. The median cancer-specific survival and 5-year overall survival were significantly lower in PD-L1+ patients. Age, gender, HIV status, HIV viral load, stage, and cancer progression were not significantly different between the two groups. CD4 count of more than 200/μL was significantly higher in PD-L1+ patients. PD-L1+ status remained statistically significant for worse overall survival on multivariate analysis. Conclusions.— PD-L1+ status is an independent adverse prognostic factor for overall survival in ASCC. This study highlights the potential of PD-L1 targeted therapy in better management of ASCC.


2021 ◽  
pp. FSO691
Author(s):  
Jii Bum Lee ◽  
Beung-Chul Ahn ◽  
Seung Hyun Kim ◽  
Young Han Lee ◽  
Jung Woo Han ◽  
...  

Aim: There are limited data on the feasibility of programmed death ligand-1 (PD-L1) expression as a prognostic biomarker in metastatic angiosarcoma. Patients & methods: We retrospectively collected and analyzed the data on PD-L1 expression in 70 angiosarcoma patients who were diagnosed at our center between 2005 and 2019. Results: Thirteen (19%) patients had PD-L1 expression. Metastatic angiosarcoma patients who were PD-L1-negative (n = 24) showed longer median progression-free survival (4.9 vs 1.6 months; p = 0.04) and median overall survival (OS; 10.9 vs 5.4 months; p = 0.01) than those who were PD-L1-positive (n = 4). PD-L1 status proved to be a significant factor for OS. Conclusion: Metastatic angiosarcoma patients with PD-L1 expression showed shorter survival. PD-L1 status is an independent prognostic factor for OS in metastatic angiosarcoma patients.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 610-610 ◽  
Author(s):  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Nobuyuki Mizunuma ◽  
Eiji Shinozaki ◽  
Mariko Ogura ◽  
...  

610 Background: In our previous report, addition of bevacizumab (BV) to the FOLFOX4 regimen appeared to significantly improve response rate, progression-free survival and overall survival in first-line treatment for patients with metastatic colorectal cancer (mCRC) (Suenaga M, et al. ASCO-GI 2011 [abstr 588]). Update results met median overall survival, and statistical analysis of survival was performed. Methods: An observational cohort study was carried out on all eligible patients scheduled to receive FOLFOX4 (n = 128) or FOLFOX4+BV (n = 85) between 2005 and 2007, 2007 and 2009, with a median follow-up time of 20.4 months vs. 30.2 months, respectively. Predefined efficacy endpoints were treatment characteristics, response rates, progression-free survival, and overall survival in the periods of time observed. Results: Median progression-free survival was 9.9 months (95% CI, 8.4-11.4) in the FOLFOX4- and 17 months (95% CI, 11.8-22.3) in the FOLFOX4+BV-treated patients (p=0.002). Median overall survival times were 20.5 months (95% CI, 16.9-24) and 38.8 months (95% CI, 32.9-44.8) in the two groups, respectively (p<0.001). In the ECOG PS 0 population, progression-free survival in the FOLFOX4 and FOLFOX4+BV groups was 11 months and 17 months with a hazard ratio of 0.63 (95% CI, 0.44-0.89) in favour of FOLFOX4+BV, similarly in OS with a hazard ratio of 0.53 (95% CI, 0.36-0.77). Subgroup population received 5-FU plus leucovorin (FL) as maintenance during oxaliplatin discontinuation due to adverse events had longer PFS or OS in both groups, though no significance. PFS were 14.7 and 21.6 months, and OS were 29 and 45.9 months, respectively. Secondary resection was performed more in FOLFOX4+BV (11.8%) than FOLFOX4 (3.9%) patients. Conclusions: These data indicate potential survival benefits from the addition of BV to the FOLFOX4 regimen as first-line treatment for mCRC. Maintenance using FL after discontinuation of oxaliplatin due to adverse events appeared to be an essential factor for better survival.


Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 421 ◽  
Author(s):  
Teresa Steinbichler ◽  
Madeleine Lichtenecker ◽  
Maria Anegg ◽  
Daniel Dejaco ◽  
Barbara Kofler ◽  
...  

Background: Following first-line treatment of head and neck cancer (HNC), persistent disease may require second-line treatment. Methods: All patients with HNC treated between 2008 and 2016 were included. Second-line treatment modalities and survival of patients were analyzed. Results: After first-line therapy, 175/741 patients had persistent disease. Of these, 112 were considered eligible for second-line treatment. Second-line treatment resulted in 50% complete response. Median overall survival of patients receiving second-line therapy was 24 (95% CI: 19 to 29) months; otherwise survival was 10 (9 to 11; p < 0.0001) months. Patients receiving second-line surgery had a median overall survival of 45 (28 to 62) months, patients receiving second-line radiotherapy had a median overall survival of 37 (0 to 79; p = 0.17) months, and patients receiving systemic therapy had a median overall survival of 13 (10 to 16; p < 0.001) months. Patients with persistent HNC in the neck had a better median survival (45 months; 16 to 74 months; p = 0.001) than patients with persistence at other sites. Conclusion: Early treatment response evaluation allows early initiation of second-line treatment and offers selected patients with persistent disease a realistic chance to achieve complete response after all. If possible, surgery or radiotherapy are preferable.


Immunotherapy ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 1067-1075
Author(s):  
Jiahao Li ◽  
Tiantian Zhang ◽  
Yongmei Xu ◽  
Peiyao Lu ◽  
Jiaxin Zhu ◽  
...  

Aim: To evaluate the cost–effectiveness of nivolumab plus ipilimumab (NI) in the first-line treatment of patients with advanced non-small-cell lung cancer from a US-payer perspective. Materials & methods: We developed a Markov model to evaluate the cost and effectiveness of NI versus chemotherapy as first-line treatment of NSCLC. Quality-adjusted life-years (QALYs) and incremental cost–effectiveness ratios (ICERs) were estimated. Results: NI provided an additional 0.715 QALYs compared with chemotherapy in all population. The corresponding ICER of NI was $180,307 per QALY gained. However, the ICER decreased to $143,434 per QALY in the programmed death ligand 1 expression level <1% population. Conclusion: From a US-payer perspective, NI is estimated to be cost-effective in the first-line setting for advanced NSCLC patients with programmed death ligand 1 expression level <1%.


Liver Cancer ◽  
2022 ◽  
Author(s):  
Sabrina Welland ◽  
Catherine Leyh ◽  
Fabian Finkelmeier ◽  
André Jefremow ◽  
Kateryna Shmanko ◽  
...  

Background Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria. Methods A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed. Results Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC. Conclusion Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.


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