Proton pump inhibitors (PPIs) and survival outcomes in patients with metastatic renal cell carcinoma (mRCC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 493-493
Author(s):  
Aly-Khan A. Lalani ◽  
Rana R. McKay ◽  
Xun Lin ◽  
Ronit Simantov ◽  
Marina D. Kaymakcalan ◽  
...  
Keyword(s):  
Adverse Events ◽  
Kinase Inhibitors ◽  
Cox Regression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Pooled Analysis ◽  
Cancer Targeting ◽  
Targeting Therapy ◽  
The Impact

493 Background: PPIs are potent inhibitors of gastric acid secretion and can affect the bioavailability of orally administered cancer targeting therapies, such as vascular endothelial growth factor tyrosine-kinase inhibitors (VEGF-TKIs). Smaller preclinical and clinical studies have attempted to assess the interaction between VEGF-TKIs and PPIs in patients with advanced cancers; however, these studies are limited and larger analyses from rigorous datasets have been lacking. We investigate the impact of PPI use on survival in patients with mRCC treated with oral VEGF-TKIs. Methods: A pooled analysis of mRCC patients treated on phase II and III clinical trials was conducted. The primary outcome was to assess overall survival (OS) between PPI users, defined as patients receiving a PPI at baseline, compared to non-PPI users. Secondary outcomes included progression-free survival (PFS), objective response rates (ORR), and adverse events. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method. Results: Our cohort consisted of 2,188 patients treated with sunitinib (n = 952), axitinib (n = 626), or sorafenib (n = 610), of whom 120 were PPI users. Overall, PPI users demonstrated similar OS compared to non-PPI users (median 24.1 vs. 21.3 months, adjusted hazard ratio [aHR] 1.051, 95% confidence interval (CI) 0.769-1.438, p = 0.754). Similarly, PFS (5.5 vs. 8.0 months, aHR 1.016, 95% CI 0.793-1.301, p = 0.902) and ORR (23.3% versus 27.4%, p = 0.344) were not different between PPI users and non-users. These findings were consistent across International mRCC Database Consortium risk groups and by line of therapy. Adverse events were also similar between both groups. Conclusions: In this analysis, we demonstrate that PPI use does not appear to negatively impact the efficacy of VEGF-TKIs in mRCC patients treated in the targeted therapy era. Given the current landscape expanding to include more self-administered treatments, documentation of concomitant medications, and patient education on potential drug interactions are critical for optimizing the utilization of oral cancer targeting therapy.

The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21587-e21587
Author(s):  
Ting Ye ◽  
Jieying Zhang ◽  
Xinyi Liu ◽  
Mengmei Yang ◽  
Yuhan Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Predictive Value ◽  
Cox Regression ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Cox Regression Analysis ◽  
Melanoma Patients ◽  
The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

Addition of Bevacizumab to Fluorouracil-Based First-Line Treatment of Metastatic Colorectal Cancer: Pooled Analysis of Cohorts of Older Patients From Two Randomized Clinical Trials

2009 ◽  
Vol 27 (2) ◽  
pp. 199-205 ◽  
Author(s):  
Fairooz F. Kabbinavar ◽  
Herbert I. Hurwitz ◽  
Jing Yi ◽  
Somnath Sarkar ◽  
Oliver Rosen
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Older Patients ◽  
Statistical Power ◽  
Randomized Clinical Trials ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
First Line ◽  
Younger Patients

PurposeColorectal cancer (CRC) occurs predominantly in older persons. To provide more statistical power to assess risk/benefit in older patients, we examined the clinical benefit of bevacizumab (BV) plus fluorouracil-based chemotherapy in first-line metastatic CRC (mCRC) treatment in patients aged ≥ 65 years, using data pooled from two placebo-controlled studies.Patients and MethodsPooled efficacy data for 439 patients ≥ 65 years old randomized to BV plus chemotherapy (n = 218) or placebo plus chemotherapy (n = 221) in study 1 and study 2 were retrospectively analyzed on an intent-to-treat basis for overall survival (OS), progression-free survival (PFS), and objective response. Safety analysis was based on reports of targeted adverse events in treated patients.ResultsMedian OS with BV plus chemotherapy was 19.3 v 14.3 months with placebo plus chemotherapy (hazard ratio [HR] = 0.70; 95% CI, 0.55 to 0.90; P = .006). Patients treated with BV plus chemotherapy had a median PFS of 9.2 v 6.2 months for placebo plus chemotherapy patients (HR = 0.52; 95% CI, 0.40 to 0.67; P < .0001). The objective response rate was 34.4% with BV plus chemotherapy versus 29.0% with placebo plus chemotherapy (difference not statistically significant). Rates of BV-associated adverse events in the pooled BV plus chemotherapy group were consistent with those reported in the overall populations for the two studies.ConclusionAnalysis of pooled patient cohorts age ≥ 65 years from two similar trials in mCRC indicates that adding bevacizumab to fluorouracil-based chemotherapy improved OS and PFS, similar to the benefits in younger patients. Also, the risks of treatment do not seem to exceed those in younger patients with mCRC.

scholarly journals The efficacy and adverse events of anlotinib plus PD-1 inhibitor for metastatic solid tumors

2021 ◽  
Author(s):  
Hao Lin ◽  
Tao Liu ◽  
Xinli Zhou ◽  
Xiaohua Liang
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Kinase Inhibitors ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Kaplan Meier ◽  
Hemorrhagic Events ◽  
Tumor Immune Microenvironment

Abstract Background Several antiangiogenic tyrosine kinase inhibitors (TKIs) have the potential to modulate the tumor immune microenvironment and improve immunotherapy effect Of these, anlotinib has demonstrated antitumor efficacy in clinical trials. However, its role in immune regulation and the potential synergistic antitumor effect of its combination with PD-1 inhibitor remain unclear. This study investigated the efficacy and adverse events (AEs) of the combination of anlotinib and PD-1 inhibitor for solid tumors in real-world settings. Methods This retrospective study included patients with metastatic solid tumors treated with anlotinib plus PD-1 inhibitor at Huashan hospital, Fudan University between October 1, 2018 and August 31, 2020. The objective response rate was assessed using the response evaluation criteria in solid tumors v1.1. Descriptive statistics were performed using the Kaplan–Meier method, and any AEs were noted. Results Partial response was achieved in 13 patients, and 8 patients showed stable disease, representing a response rate of 43.3% and a disease control rate of 70%. The median progression-free survival was 3.8 months. Although AEs were observed in 50% of patients, most of them were Grades 1–2 and well tolerated. The most common AEs were thrombocytopenia (16%), thromboembolic or hemorrhagic events (16%), and rash (13%). Conclusions Anlotinib plus PD-1 inhibitor is an alternative salvage treatment choice in metastatic solid tumors with Favorable efficacy and tolerable toxicities.

Prognostic significance of bone metastases (BM) and bisphosphonate (BIS) therapy in patients with metastatic renal cell carcinoma (mRCC) treated with molecularly targeted agents (MTAs).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4572-4572
Author(s):  
Rana R. McKay ◽  
Xun Lin ◽  
Julia Jane Perkins ◽  
Ronit Simantov ◽  
Toni K. Choueiri
Keyword(s):  
Cox Regression ◽  
Positive Impact ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Impact On Survival ◽  
Ecog Ps ◽  
The Impact

4572 Background: BM are frequently present in patients with mRCC. BM cause significant morbidity and are associated with high rates of skeletal related events (SREs). The purpose of this retrospective analysis was to assess the impact of BM and BIS use on outcomes including progression-free survival (PFS) and overall survival (OS) in patients with mRCC. Methods: We conducted a pooled analysis of patients with mRCC treated from 2003-2011 on phase III (NCT00083899, NCT00065468, NCT00678392) and phase II trials (NCT00054886, NCT00077974, NCT00083889, NCT00338884, NCT00137423). Statistical analyses were performed using Cox regression and the Kaplan-Meier method. Results: We identified 2,749 patients treated with sunitinib (n=1,059), sorafenib (n=335), axitinib (n=359), temsirolimus (TEM) (n=208), TEM + interferon-alfa (IFN) (n=208), or IFN (n=560). Most patients were male (71%), had baseline ECOG PS of 0 (47%) or 1 (51%), clear cell histology (91%), and prior nephrectomy (84%). 285 patients (10.4%) received treatment with BIS (zoledronic acid n=233, pamidronate n=57, unspecified n=1). No patients received denosumab. Of the 2,504 patients with data regarding site of metastasis at diagnosis, 31.9% (n=781) had BM. The rate of SREs in patients with BM compared to patients without BM was 6.4% versus 1.4% (p<0.0001). Presence of BM was associated with shorter PFS (5.1 vs. 6.7 months (mo), HR 1.195, 95% CI 1.076-1.328, p<0.0008) and OS (13.2 vs. 20.2 mo, HR 1.292, 95% CI 1.145-1.456, p<0.0001) when compared to those without BM. In patients with BM, the use of BIS was not associated with improved PFS (5.1 vs. 4.9 mo, HR 0.867, 95% CI 0.704-1.067, p=0.1785) or OS (13.3 vs. 13.1 mo, HR 0.904, 95% CI 0.722-1.132, p=0.3801) when compared to patients who did not receive BIS. In patients with BM stratified by type of first-line MTA (TKI, mTOR inhibitor, or IFN-based), use of BIS was not associated with improved PFS or OS. Conclusions: In this analysis, we confirm that the presence of BM is an adverse risk factor for shorter PFS and OS in patients with mRCC treated with MTAs. Treatment with BIS did not have a positive impact on survival in this cohort.

Heterogeneity of intermediate prognosis patients (pts) with metastatic renal cell cancer (mRCC) treated with sunitinib.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 446-446
Author(s):  
Avishay Sella ◽  
M. Dror Michaelson ◽  
Ewa M. Matczak ◽  
Ronit Simantov ◽  
Mariajose Lechuga ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kinase Inhibitors ◽  
Risk Model ◽  
Cox Regression ◽  
Performance Status ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Ecog Performance Status

446 Background: The Memorial Sloan Kettering Cancer Center risk model (MSKCC) stratifies pts with mRCC into 3 prognostic groups based on 5 risk factors. The Intermediate Prognosis (INTMP) risk group is characterized by the presence of 1 or 2 factors, equivalent to 15 possible distinct entities. This heterogeneity suggests that the efficacy of tyrosine kinase inhibitors may be less predictable in the INTMP than in the other groups. Methods: We identified 548 patients with INTMP mRCC from a pooled analysis of patients treated with sunitinib in 6 prospective phase II and III clinical trials. Statistical analysis was performed using Cox regression and Kaplan-Meier methods and Pearson chi-square tests. Results: Most INTMP pts were male (69%), with clear cell carcinoma (93%), good ECOG performance status (PS) (60.5% PS 0; 38% PS 1; 1.5% PS 2) and median age 60. There were 325 pts (56%) with 1risk factor, and the most common were <1 year from diagnosis (38%); low hemoglobin (Hg) (29%), or both (16%). Objective response rate (RR) was 35.4%, progression free survival (PFS) was 8.4 months (m) and overall survival (OS) was 20.5 m. The 325 (59.3%) pts with one risk factor fared better than the 223 (40.7%) patients with two: PFS 10.7 vs 6.5 m, HR 0.684(95% CI 0.563-0.832, p<0.001); OS 26.3 vs 14.1 m, HR 0.522 (95% CI 0.420-0.648, p<0.001). RR was similar (38.5% vs 30.9%, p=0.071). Sunitinib was more effective in pts with PS 0: PFS 9.7 vs 7.8 m, HR 0.797 (95% CI 0.654-0.972, p=0.0242); OS 24.7 vs 14.0 m, HR 0.529 (95% CI 0.426-0.657, p<0.001), RR 38.9% vs 30.1%, (p=0.036). The most common grade 3/4 adverse events (AE) were fatigue (17%), hypertension (10%), hand foot skin reaction (9%), and nausea (4%). Overall, 17% of patients discontinued due to AE, and the overall pattern of AEs did not vary among the subgroups. Conclusions: MSKCC INTMP is a heterogeneous group comprised mostly of pts with low Hg and/or < 1 year from diagnosis. PFS and OS are superior in pts with 1 vs. 2 risk factors, and PS is also an important factor in the INTMP group. Sunitinib is active and well-tolerated in INTMP pts. Clinical trial information: NCT00077974, NCT00083889, NCT00137423, NCT00267748, NCT00338884, NCT00054886.

Antibiotic use and outcomes with systemic therapy in metastatic renal cell carcinoma (mRCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 607-607 ◽  
Author(s):  
Aly-Khan A. Lalani ◽  
Wanling Xie ◽  
Xun Lin ◽  
John A. Steinharter ◽  
Dylan J. Martini ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Risk Groups ◽  
Antibiotic Use ◽  
Vegf Inhibitors ◽  
Logistic Regression Models ◽  
The Impact

607 Background: Antibiotic (Abx) use is shown to alter commensal gut microbiota, a key regulator of immune homeostasis. We conducted the largest investigation to date on the impact of Abx use on outcomes in mRCC patients treated with systemic agents. Methods: Two cohorts were analyzed: an institutional cohort (DFCI, n = 146) of patients receiving PD-1/PD-L1-based immune checkpoint inhibitors (ICI), and an external cohort from pooled phase II/III clinical trials (Pfizer, n = 4144) of patients treated with interferon (IFN, n = 510), mTOR inhibitors (n = 660), and VEGF inhibitors (n = 2974). Abx use was defined as Abx treatment at any time between 8-weeks pre- and 4-weeks post the start of systemic therapy. We examined the associations of Abx use and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) using Cox/logistic regression models, adjusted for prognostic factors including risk groups. Results: In the DFCI cohort, 15% had non-clear cell histology, 43% had first-line ICI, 45% had combotherapy. Baseline characteristics were balanced between Abx users (n = 31, 21%) and non-users (p > 0.15). Abx users had a lower ORR (12.9 vs 34.8%, p = 0.026) and shorter PFS compared to non-users (Table). In the external cohort, Abx users (n = 709) had lower ORR (19.3 vs 24.2%, p = 0.005). IFN treated patients (current or prior cytokines) had worse OS if they received Abx compared to those who did not. However, there was no OS difference by Abx use in mTOR or VEGF treated patients without prior cytokines. Conclusions: Abx use was independently associated with worse outcomes in mRCC patients receiving contemporary ICI or historic cytokine immunotherapy. We hypothesize that concurrent use of Abx may reduce the efficacy of ICI due to a complex interplay with the host microbiome. [Table: see text]

scholarly journals Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhe Zhao ◽  
Xinfeng Wang ◽  
Jinghan Qu ◽  
Wei Zuo ◽  
Yan Tang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Pooled Analysis ◽  
Conclusive Evidence ◽  
Risk Of Death

Background and ObjectiveAlthough anti-programmed cell death protein 1 (PD-1) antibodies have exerted remarkable anticancer activity in non-small cell lung cancer (NSCLC), it remains a challenge to identify patients who can benefit from these treatments. Immune-related adverse events (irAEs) may be associated with improved clinical outcomes after immune checkpoint inhibition. However, no conclusive evidence of this correlation has been summarized in patients with NSCLC receiving PD-1 inhibitors. We performed a systematic review and meta-analysis to evaluate the association between irAEs induced by anti-PD-1 antibodies and clinical outcomes in patients with NSCLC.MethodsVarious databases were searched from their inception to January 9, 2021, followed by screening of eligible studies. Hazard ratios were used for the pooled analysis of overall survival (OS) and progression-free survival (PFS), while odds ratios (ORs) were utilized to pool objective response rates (ORRs) and disease control rates (DCRs). A random-effects model was applied to all analyses.ResultsA total of 26 cohorts, including 8,452 patients with NSCLC receiving anti-PD-1 antibodies, were enrolled in the study. Significantly improved OS (HR: 0.51; 95% CI: 0.44-0.60; P &lt; 0.01) and PFS (HR: 0.50; 95% CI: 0.43-0.58; P &lt; 0.01) were found to be correlated with irAEs. In addition, patients with NSCLC who developed irAEs after PD-1 inhibition demonstrated better responses to therapies, confirmed by pooled ORs of ORRs (OR: 3.41; 95% CI: 2.66-4.35; P &lt; 0.01) and DCRs (OR: 4.08; 95% CI: 2.30-7.24; P &lt; 0.01). Furthermore, subgroup analysis suggested that both skin and endocrine irAEs are closely correlated with a reduced risk of death, whereas pulmonary irAEs showed no association with longer OS.ConclusionsIn patients with NSCLC treated with anti-PD-1 therapies, the presence of irAEs was strongly correlated with better survival and response, suggesting its potential role as a predictive biomarker for outcomes after PD-1 inhibition.

scholarly journals The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma

2022 ◽  
Vol 12 ◽  
Author(s):  
Ting Ye ◽  
Jie-Ying Zhang ◽  
Xin-Yi Liu ◽  
Yu-Han Zhou ◽  
Si-Yue Yuan ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Independent Predictive Factor ◽  
Cox Regression Analysis ◽  
Melanoma Patients ◽  
The Impact

BackgroundMAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response.MethodsSix metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation.ResultsCompared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment.ConclusionsMAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.

scholarly journals Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials

2017 ◽  
Vol 35 (34) ◽  
pp. 3807-3814 ◽  
Author(s):  
Dirk Schadendorf ◽  
Jedd D. Wolchok ◽  
F. Stephen Hodi ◽  
Vanna Chiarion-Sileni ◽  
Rene Gonzalez ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Advanced Melanoma ◽  
Induction Phase ◽  
Efficacy And Safety ◽  
Grade 3 ◽  
Phase Ii And Iii

Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231). Results At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs ( P = .97). Median overall survival had not been reached in either group ( P = .23). The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy.

Impact of body mass index (BMI) on treatment outcomes to immune checkpoint blockade (ICB) in metastatic renal cell carcinoma (mRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 566-566 ◽  
Author(s):  
Aly-Khan A. Lalani ◽  
Wanling Xie ◽  
Ronan Flippot ◽  
John A. Steinharter ◽  
Lauren Christine Harshman ◽  
...  
Keyword(s):  
Cox Regression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Obesity Paradox ◽  
Immune Checkpoint Blockade ◽  
Normal Weight ◽  
First Line ◽  
Line Of Therapy ◽  
High Bmi

566 Background: An elevated BMI is associated with improved survival in mRCC patients treated with oral targeted therapies (TT); however, this relationship in the contemporary treatment landscape is unknown. We investigated the effect of BMI on outcomes in mRCC patients treated with PD-1/PD-L1 ICB. Methods: We analyzed 147 patients with mRCC who received ICB alone or in combination with VEGF or other therapies. The association of BMI with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was evaluated using logistic and Cox regression models, adjusted for known prognostic factors including International Metastatic RCC Database Consortium (IMDC) risk groups, line of therapy, ECOG (0 vs ≥1), and histology. Results: Median follow up was 25.5 (4.3-78.6) months (mos). Median time on ICB was 5.1 ( < 0.1-69.7) mos. Overall, most patients were male (71%), had clear cell histology (85%), and were intermediate risk (60%). 43% received first-line ICB and 45% received ICB in combination therapy (37% with VEGF inhibition, 8% with other therapies). At ICB initiation, 46 (31%) patients were considered underweight/normal weight (BMI < 25 kg/m2), 56 (38%) overweight (BMI 25-30 kg/m2), and 45 (31%) obese (BMI > 30 kg/m2). Patients with high BMI (≥ 25) had improved OS (median 34.3 vs 16.7 mos, 2-yr OS 61 vs 42%, p = 0.016) compared to those with low BMI ( < 25), with an adjusted hazard ratio (HR) = 0.74 (0.44-1.26). ORR (33 vs 28%, p = 0.7) and PFS (median 8.2 vs 5.9 mos, p = 0.4) did not statistically differ. Patients who experienced a BMI change from ≥ 25 at start of first-line TT to < 25 at start of subsequent-line ICB displayed shorter OS (adjusted HR = 2.25 (0.94-5.35)) compared to those with no change. Conclusions: High BMI appears to be associated with improved OS in mRCC patients treated with ICB. This contemporary data is consistent with the “obesity paradox” demonstrated in the TT era. Validation with the IMDC database and examination of underlying mechanisms are ongoing.

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