Analysis of age, tumor-sidedness, and mismatch repair (MMR) genes with response to immune checkpoint inhibitors (ICIs) in MMR-deficient (dMMR) colorectal cancer (CRC) patients (pts): A multi-institutional study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15029-e15029
Author(s):  
Ibrahim Halil Sahin ◽  
Wanqi Chen ◽  
Mohamad Bassam Sonbol ◽  
Satya Das ◽  
Zhengjia Chen ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Braf Mutations ◽  
Exact Test ◽  
Mmr Genes ◽  
Cox Proportional Hazard ◽  
Predictors Of Response ◽  
Best Response ◽  
Emory University ◽  
The Impact

e15029 Background: ICIs induce durable responses in dMMR CRC pts with overall response rates (ORR) of 30-50%. Even though the loss of expression of any MMR gene predicts ICIs response, it is unknown if ORRs are similar across all MMR genes (MLH1, PMS2, MSH2, and MSH6). In this study, we analyzed the impact of each specific MMR gene loss and clinical characteristics of pts with best response to ICIs. Methods: Pts were eligible if they had confirmed dMMR CRC by IHC or microsatellite instability-high (MSI-H) by PCR, and received ICIs between 01/01/2012 and 10/01/2018 at Winship Cancer Institute of Emory University, Mayo Clinic or Vanderbilt University Medical Center. Due to the pattern of frequent concurrent loss and functional dependency, the groups were categorized as MLH1 ±PMS2 vs. MSH2 ±MSH6. Cox proportional hazard model and Fisher’s exact test were used for the best response and the distribution of variable among the subgroups. Results: A total of 45 pts with dMMR CRC were identified. ORRs in MLH1 ±PMS2 and MSH2 ±MSH6 groups were 68% and 57.1% respectively without statistical difference (Table). Pts with age < 50 and 50-65 years old had better ORRs compared to pts with age >65 (58.3%, 85.7% and 42.1% respectively, P=0.036). Left-sided tumors had a trend toward higher ORRs compared to right-sided tumors (83.3% vs 51.5% P=0.086). Gender and BRAF status were not predictors of response. BRAF mutations were more common in right-sided tumors (29.6% vs 11.1% respectively) and in older patients. Conclusions: Our data suggest that MSI-H CRC pts aged 50-65 treated with ICIs, have improved ORR compared to pts > 65; pts with left-sided tumors have a trend toward improved ORR compared to those with right sided tumors. [Table: see text]

The impact of pretreatment absolute lymphocyte count (pALC) and neutrophil-lymphocyte ratio (pNLR) on checkpoint inhibitors (CPIs) response rates in renal cell carcinoma (RCC) and bladder urothelial cancers (BC).

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 29-29
Author(s):  
Tonjeh Mary Stella Bah ◽  
David Sommerhalder ◽  
Philip A. Haddad
Keyword(s):  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Response Rates ◽  
Neutrophil Lymphocyte Ratio ◽  
Essential Components ◽  
Group A ◽  
Group 2 ◽  
Group B ◽  
The Impact ◽  
Group 1

31 Background: CPIs have been established as essential components of cancer immunotherapy across multiple cancer types with proven clinical benefit, improved outcomes, and less toxicity. Studies in lung and head and neck cancers found that low ALC, a marker of immune exhaustion, was associated with poor response to CPIs and worse progression-free survival. We explored the effect of pALC and pNLR on CPI response rates in patients with RCC and BC. Methods: We retrospectively reviewed every RCC and BC patient that received CPIs at Overton Brooks VA Medical Center and LSUHSC-S between 2015 and 2019. Patients’ pALC and pNLR were calculated. The patients were divided according to pALC into 2 groups: Group A with pALC > 1000 and Group B with pALC < 1000. Similarly, using NLR’s established upper normal limit of 3, 2 groups were created: Group 1 with pNLR < 3 and Group 2 with pNLR > 3. Our primary outcome of interest was defined as the presence or absence of CPI response. Patients who attained stable disease, partial response, and complete response were categorized as responders. Those who progressed on CPIs were labeled as non-responders. The significance of the association between pALC and pNLR groups and the occurrence of any response was analyzed statistically. Results: Twenty patients (13 RCC, 7 BC) were treated with CPIs and had documented responses. Twelve patients had pALC > 1000 (Group A) whereas 8 patients had pALC < 1000 (Group B). Both groups were comparable with respect to age, sex, race, and types of CPIs. Group A had a significantly higher response rate (75% vs 25%, p = 0.027). As to pNLR, 10 patients had pNLR < 3 (Group 1) and another 10 patients had pNLR > 3 (Group 2). Patients with pNLR > 3 had worse response rates to CPIs compared to those with pNLR < 3 (30% vs 80%, p = 0.024). Conclusions: This is the first report from a real-world clinical setting to show a detrimental association between pALC < 1000 and pNLR > 3 and CPI response rates in a retrospective cohort of consecutive non-selected kidney and bladder cancer patients. This association and its clinical utility require further confirmation in a prospective larger cohort.

Impact of concurrent ACE inhibitors and ARBs on outcomes with immune-checkpoint inhibitors (ICIs) for patients (pts) with metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 354-354
Author(s):  
Pier Vitale Nuzzo ◽  
Catherine Curran ◽  
Elio Adib ◽  
Dory Freeman ◽  
Amin Nassar ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Transforming Growth Factor ◽  
Checkpoint Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
P Value ◽  
Line Treatment ◽  
Concurrent Administration ◽  
Best Response ◽  
The Impact

354 Background: The renin-angiotensin system (RAS) is involved in regulation of angiogenesis and cell proliferation and may improve drug delivery by enhancing tumor perfusion partly by downregulating transforming growth factor (TGF)-β. Since (TGF)-β appears to be associated with resistance in patients receiving immune checkpoint inhibitors (ICIs), we investigated whether angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) may enhance the outcomes of mRCC pts receiving ICI. Methods: Data from mRCC pts who received ICIs at the Dana-Farber Cancer Institute (DFCI) was obtained. Data for ACEI and ARB administration was collected with concurrent administration defined as ongoing therapy from the time of starting ICI . The Kaplan-Meier method and Cox were used to evaluate the impact of concurrent ACEI/ARB on overall survival (OS). Results: Data was available for 134 pts. The mean age was 63 years (Range 37-85)). 94 (70%) pts were male. The therapies included Nivolumab+/-Other (104), Atezolizumab+/-Other (21), Pembrolizumab+/-Other (8) and Durvalumab +Tremelimumab (1). 35 (25%) pts received ICI as first line treatment, 52 (39%) received as second line treatment, and 48 (36%) received as third line or higher. Out of the 134 pts, 39 (29%) had been treated with an ACEI or ARB during ICI treatment. Out of the 39 pts who had ACEI or ARB, 2 (5%) had complete response (CR) as best response, 11 (28%) had partial response (PR), 17 (46%) had stable disease (SD) and 9 (23%) had progressive disease (PD). Out of the 95 pts who did not receive ACEI or ARB, 3 pts (3%) had CR as their best response to ICI, 19 (21%) had PR, 39 (43%) had SD, and 29 (32%) had PD, (5 patients’ best response were unevaluable). The median OS for those who had ACEI/ARBs and did not have ACEI/ARBs was 32 months and 20 months respectively. Univariable analysis revealed that patients who received ACEI/ARBs had improved OS (Logrank p-value = 0.002; HR = 2.5 [95%CI: 1.4 - 4.5]). Conclusions: In this hypothesis-generating study, concurrent ACEI/ARBs are associated with better outcomes for mRCC pts receiving ICIs. Given the availability of ACEI/ARBs, it is important to validate this result in a larger dataset and after controlling for known prognostic factors.

scholarly journals The impact of sequencing PD-1/PD-L1 inhibitors and stereotactic radiosurgery for patients with brain metastasis

2019 ◽  
Vol 21 (8) ◽  
pp. 1060-1068 ◽  
Author(s):  
Rupesh Kotecha ◽  
Joseph M Kim ◽  
Jacob A Miller ◽  
Aditya Juloori ◽  
Samuel T Chao ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Checkpoint Inhibitors ◽  
Combined Modality Therapy ◽  
Objective Response ◽  
Complete Response ◽  
Substantial Effect ◽  
Durable Response ◽  
Best Response ◽  
Programmed Cell Death 1 ◽  
The Impact

Abstract Background The response of brain metastases (BM) treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs; programmed cell death 1 and its ligand) is of significant interest. Methods Patients were divided into cohorts based on ICI sequencing around SRS. The primary outcome was best objective response (BOR) that was lesion specific. Secondary outcomes included overall objective response (OOR), response durability, radiation necrosis (RN), and overall survival (OS). Results One hundred fifty patients underwent SRS to 1003 BM and received ICI. Five hundred sixty-four lesions (56%) treated with concurrent ICI (±5 half-lives) demonstrated superior BOR, OOR, and response durability compared with lesions treated with SRS and delayed ICI. Responses were best in those treated with immediate (±1 half-life) ICI (BOR: −100 vs −57%, P < 0.001; complete response: 50 vs 32%; 12-month durable response: 94 vs 71%, P < 0.001). Lesions pre-exposed to ICI and treated with SRS had poorer BOR (−45%) compared with ICI naive lesions (−63%, P < 0.001); best response was observed in ICI naive lesions receiving SRS and immediate ICI (−100%, P < 0.001). The 12-month cumulative incidence of RN with immediate ICI was 3.2% (95% CI: 1.3–5.0%). First radiographic follow-up and best intracranial response were significantly associated with longer OS; steroids were associated with inferior response rates and poorer OS (median 10 vs 25 mo, P = 0.002). Conclusions Sequencing of ICI around SRS is associated with overall response, best response, and response durability, with the most substantial effect in ICI naive BM undergoing immediate combined modality therapy. First intracranial response for patients treated with immediate ICI and SRS may be prognostic for OS, whereas steroids are detrimental.

Frequency and prognostic role of tumor infiltrating lymphocytes and MMR status in advanced non-colorectal GI malignancies.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 89-89
Author(s):  
Uqba Khan ◽  
Ameer Hamza ◽  
Renny Abraham ◽  
Muhammad S Khurram ◽  
Tarik H. Hadid ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Tumor Infiltrating Lymphocytes ◽  
Mismatch Repair Gene ◽  
High Power Field ◽  
Repair Gene ◽  
Number Of Patients ◽  
Significant Difference ◽  
Infiltrating Lymphocytes ◽  
The Impact

89 Background: Tumor infiltrating lymphocytes (TILs) and mismatch repair gene mutation (MMR) status are emerging biomarkers in immunotherapy. MMR status and TILs have significant clinical implications with respect to treatment with checkpoint inhibitors. We designed a study to determine the frequency and prognostic utility of TILs and MMR in advanced unresectable non-colorectal GI (NCGI) cancers. Methods: This is a retrospective cohort study of patients who were diagnosed with metastatic or unresectable NCGI cancers between 2009 and 2015 at St. John Hospital and Medical Center. Immunohistochemistry panels were performed on representative tissue sections for MMR testing. TILs were assessed on the hematoxylin and eosin stained slide of the same tissue section. MMR was interpreted as deficient (d) or proficient and TILs were categorized as ≤5 or > 5 per high power field. Descriptive statistics were generated using frequency distributions, medians and means. Kaplan-Meier analysis was performed to determine the impact of TILS and MMR on survival; differences by factor were assessed with the Log_Rank test. Results: We analyzed 132 patients; the mean age at diagnosis was 66.7 years, 62.1% were male. All samples had proficient MMR status. The percentage of patients with TILs ≤ 5 was 46.2. There was no statistically significant difference in median overall survival (OS) by TILs when stratified by stage of tumor. When stratified by type of tumor, median OS by TILs level was significantly different only for hepatocellular cancers (HCC) (≤ 5 TILs, 86 days vs. > 5 TILs 312 days, p = 0.031), table 1. Conclusions: Our study suggests that MMR-d tumors are quite rare in advanced NCGI malignancies. TILs can be present in tumor microenvironment of NCGI malignancies. Though the number of patients in our study was small, there was a statistically significant difference in median OS of patients with HCC when stratified by TILs status.[Table: see text]

Clinical and molecular markers of immune checkpoint inhibitor (ICI) response in dMMR colorectal cancer (CRC) patients (pts).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 225-225 ◽  
Author(s):  
Ibrahim Halil Sahin ◽  
Subir Goyal ◽  
Yoanna S Pumpalova ◽  
Mohamad Bassam Sonbol ◽  
Satya Das ◽  
...  
Keyword(s):  
Braf V600e Mutation ◽  
Braf V600e ◽  
Rank Test ◽  
Loss Of Function ◽  
Protein Loss ◽  
Exact Test ◽  
Best Response ◽  
Emory University ◽  
Cox Hazard Model ◽  
Mmr Proteins

225 Background: ICIs induce durable responses in dMMR CRC patients. However, clinical and molecular biomarkers of response to ICIs have not been well-established. In this study, we investigated impact of specific MMR gene loss, BRAF V600E mutation and clinical characteristics of pts on clinical outcomes of ICIs. Methods: Pts were eligible if they had confirmed dMMR CRC by IHC or MSI-H by PCR and received ICIs between 01/01/2012 and 05/01/2019 at Winship Cancer Institute of Emory University, Mayo Clinic, Vanderbilt or Stanford University. Due to the functional dependency, the groups were categorized as protein loss of MLH1+PMS2 vs MSH2+MSH6. Log-rank test, Cox hazard model and Fisher’s exact test were used for survival outcomes, the best response and the distribution of variables among the subgroups. Results: A total of 66 pts with dMMR CRC were identified and BRAF status was available for 41 pts. ORRs in MLH1+PMS2 and MSH2+MSH6 groups were 72.9% and 56.5% respectively (P = 0.189). At 2 years, PFS rates were 55.6% and 78.2% for MLH1+PMS2 and MSH2+MSH6 groups respectively (P < 0.001). Pts with BRAF V600E mutations had significantly worse outcomes as compared to pts with wild-type BRAF (2-year PFS rate of 35.0% and 73.3% respectively; P < 0.001). Notably pts < 65 had better 2-year disease control rates when compared to > 65 (71.1% and 41.5% respectively; P < 0.001). We also observed worse 2-year PFS rates in pts with liver metastases (P = 0.014). CRC side and tumor volume did not impact 2-year PFS rates in our cohort. Conclusions: Our data suggest that pts with loss of function in MSH2+MSH6 may have better 2 year-PFS rates compared pts with MLH1+PMS2 even though ORR favored MLH1+PMS2 group suggesting that ORR may not reflect the durability of ICI response in dMMR CRC patients. Consistently, pts with BRAF V600E mutation which is associated with MLH1 promoter methylation had significantly worse 2-year PFS rates. Overall, our findings suggest that BRAFV600E mutation, the affected MMR proteins, pt age, and site of metastasis may impact durability of ICI response in dMMR CRC patients.

Frequency and outcomes of melanoma subtypes in a diverse population: The Los Angeles County – University of Southern California (LAC-USC) Medical Center experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21063-e21063
Author(s):  
Gino Kim In ◽  
Dongyun Yang ◽  
Jacob Stephen Thomas ◽  
Anthony Pham ◽  
Arnab Basu ◽  
...  
Keyword(s):  
African Americans ◽  
Los Angeles ◽  
Medical Center ◽  
Prior History ◽  
P Value ◽  
Superficial Spreading ◽  
Braf Mutations ◽  
Exact Test ◽  
Number Of Patients ◽  
Melanoma Patients

e21063 Background: Melanoma is a biologically heterogeneous disease that varies by ethnicity and histology. While superficial spreading (SSM) histology is the most common subtype in non-Hispanic whites (NHW), acral lentiginous (ALM) and other subtypes occur more frequently in Hispanics, Asians and African Americans. There are no known risk factors for ALM, and further investigation is warranted. Methods: We retrospectively reviewed a database of melanoma patients diagnosed between 2001-2016 at LAC-USC. Overall survival (OS) was estimated using Kaplan-Meier methodology, and comparisons performed using log-rank testing. Fisher’s exact test was used to evaluate associations between relevant clinicopathological variables. A p-value < 0.05 was considered statistically significant. Results: Among 272 melanoma patients, there were 140 Hispanics (51.5%), 105 NHW (38.6%), 14 Asians, and 4 African Americans. The most frequent histology among Hispanics was ALM (30.7%), while SSM was the most frequent among NHW (33.3%). BRAF V600 mutations were found in 34.5% (10/29) and 58.8% (10/17) of Hispanics and NHW, respectively. A total of 52 patients with ALM were identified, including 43 Hispanics (82.7%). There was a significant association between no prior history of non-melanoma skin cancer (NMSC) and ALM (p < .0001). Median Breslow thickness for ALM was 4.2 mm, and 32.7% were ulcerated. The rate of BRAF V600 mutations among 13 ALM patients tested was 0%. NRAS mutations were found in 3 ALM patients; KIT amplification/mutations were found in 2 ALM patients. Conclusions: We identified a population enriched for Hispanic patients with ALM. We found an association between no prior NMSC and ALM, suggesting that UV exposure is not a causative risk factor. BRAF mutations are less common amongst Hispanics, and nearly absent in ALM. Survival differences were not statistically significant, but cannot be ruled out due to low number of patients in this early study. [Table: see text]

Frequency and prognostic utility of MSI and TILs in advanced noncolorectal GI malignancies.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 313-313
Author(s):  
Uqba Khan ◽  
Ameer Hamza ◽  
Muhammad S Khurram ◽  
Renny Abraham ◽  
Paul Mazzara ◽  
...  
Keyword(s):  
Median Survival ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Adoptive T Cell Therapy ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
T Cell Therapy ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Impact

313 Background: Mismatch repair gene mutation status not only has a role in pathogenesis but also has significant clinical implications with respect to treatment with checkpoint inhibitors. Additionally tumor infiltrating lymphocytes (TILs) are also emerging prognostic biomarker and are utilized in adoptive T-cell therapy as well. Methods: This is a retrospective cohort study of patients who were diagnosed with advanced unresectable non-colorectal GI (NCGI) cancers. Biopsy specimens of patients diagnosed between 2009 and 2015 at St. John Hospital and Medical Center were analyzed. Immunohistochemistry panels were performed on a representative tissue sections for microsatellite instability (MSI) testing. TILs were assessed on the hematoxylin and Eosin stained slide of the same tissue section. MSI was interpreted as stable or high and TILs were categorized as ≤5 and > 5 per high power field. Descriptive statistics were generated using frequency distributions, medians and means. Kaplan-Meier analysis was performed to determine the impact of TILs and MSI on survival; differences by factor were assessed with the Log_Rank test. Results: We analyzed 114 patients; the mean age at diagnosis was 66.8 ± 10.7 years, 61.4% were male. All samples were MSI stable. The percentage of patients with TILs ≤ 5 was 46.5. When stratified by tumor stage, overall median survival by TILs level did not differ significantly. When stratified by type of tumor, overall median survival by TILs level was significantly different only for hepatocellular cancers (HCC) (≤ 5 TILs, 86 days vs. > 5 TILs 312 days, p = 0.031) only, (see table). Conclusions: Our study shows that MSI-H tumors are very rare in advanced NCGI malignancies. TILs are definitely present in tumor microenvironment of NCGI malignancies. Though the number of patients of our study was small, there was a statistically significant difference in median overall survival of patients with HCC when stratified by TILs status.[Table: see text]

A prospective cohort study of HLA-B44 supertype as predictor of response to novel immune checkpoint combinations.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15071-e15071
Author(s):  
Tatiana Hernandez-Guerrero ◽  
Bernard Doger ◽  
Daniel Morillo ◽  
Victoria Casado ◽  
Manuel Domine ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Prospective Cohort ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Predictors Of Response ◽  
Early Phase Clinical Trials ◽  
Metastatic Sites ◽  
The Impact

e15071 Background: To date there are no clear predictors of response to novel immune checkpoint inhibitor (ICI) combinations. Recent reports suggest that HLA-I (Human Leukocyte Antigen Class I) supertype B44 may predict survival to PD1(L)1 inhibition in patients with melanoma and non-small cell lung cancer (NSCLC) ( Chowell et al, Science 2018). We sought to study if this effect is exclusive for PD(L)1 inhibition alone and the impact of HLA-B44 on ICI combinations with new immunotherapeutic agents. Methods: Between 2017 and 2019, 77 patients treated across 11 different early phase clinical trials (NSCLC: 64: (83,1%); melanoma: 4: (5,2%), bladder 8 (10,4%); and one nasopharynx carcinoma), ICI-naive were prospectively evaluated for HLA-I subclass. All patients were ECOG 0 or 1 (50 and 27 respectively). Most patients had ≤ 2 metastatic sites (55: 71,4%); 24 (31,2%) patients were treated with PD(L)1 inhibitors as monotherapy, and 53 (68.8%) with PD(L)1-containing combinations including ICI and agonists such as ICOS, OX40 or GITR monoclonal antibodies. HLA-I was classified for supertypes and the variables of progression-free survival (PFS) and overall survival (OS) were compared for patients with HLA-B44+ and B44-, in both groups (monotherapy and combinations). Results: 44 patients were HLA-B44+ and 33 were negative. For patients treated with anti-PD(L)1 agents as monotherapy, those that were HLA-B44+ had a longer PFS: [medianPFS: 22,38 months (m) (95% CI: 13,39 – 31,37); vs 3,8m (95% IC: 2,05 – 5,65); p: 0,002] and OS: [median: 33,2 m (95% CI: 23,7 – 42,6) vs 14,46 m (95% IC: 7,86 – 21,1); p: 0,13]. In contrast, these marked differences were not evident in patients receiving PD1 combination therapies [HLA-B44+ mPFS: 7,17m (95% CI: 4,41 - 9,93) vs 9,46 m (IC95% 6,8 m – 12,07); p:0,290], and OS: 11,53m (95% IC: 8,33 – 14,7) vs 18,9 m (IC 95% 13,3 – 24,5) p: 0,24. Lastly, response rate was also better for patients with HLA-B44 positive treated with PD1 monotherapy (66,7% vs 16,7% in HLA-B44 negative patients) p: 0,048, whilst when administering ICI combinations, HLA-B44 negative patients seemed to have a better response rate (44% vs 27% in HLA-B44 positive patients; p = 0,148). Conclusions: These results confirm in a prospective cohort the predictive impact of HLA-B44 supertype for patients treated with anti-PD(L)1 agent and suggest a potential benefit of combining checkpoint inhibitors in patients with other HLA supertypes (non-HLA-B44+).

A multicenter retrospective study to evaluate real-world clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) and brain metastasis treated with ipilimumab and nivolumab.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 637-637
Author(s):  
Landon Carter Brown ◽  
Kunal Desai ◽  
Chester Kao ◽  
Emily Noelle Kinsey ◽  
Patrick Healy ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Real World ◽  
Objective Response ◽  
Cleveland Clinic ◽  
Second Line ◽  
Exact Test ◽  
Predictors Of Response ◽  
Best Response ◽  
Line Of Therapy

637 Background: The combination of ipilimumab & nivolumab (I+N) followed by maintenance nivolumab has improved outcomes in patients (pts) with mRCC. Little is known about the outcomes in mRCC pts with brain metastasis. In this multicenter retrospective analysis, we present a real-world experience in pts with brain metastasis treated with I+N. Methods: Pts with mRCC and brain metastases treated with I+N at the Duke Cancer Institute and Cleveland Clinic were identified. Pt characteristics were summarized with descriptive statistics. Fisher’s exact test was used to determine predictors of response (alpha 0.05). Results: From 10/2017 to 2/2019, 17 pts received I+N for mRCC with brain metastases. Median age was 60; 29% were female. IMDC risk was 18%/59%/24% favorable/intermediate/poor, and 77% were clear cell histology. Pts received I+N as either first-line (65%) or ≥ second-line (35%) therapy. Of the pts evaluable for response: objective response rate (ORR) was 42% [0% CR]; with 29% achieving stable disease and 18% progressive disease as their best response. Median duration on therapy was 13 weeks. 59% of pts developed an immune-related adverse event (AE). The most common reason for treatment discontinuation was disease progression (47%) followed by AEs (18%). There were no significant predictors of any radiographic response category (PR, SD, or PD) among variables assessed (gender, IMDC risk, histology, presence of bone metastasis, line of therapy, or presence of irAE). Of note, 50% (3/6) patients treated in the second-line or greater setting experienced a PR. Conclusions: In our real-world cohort of mRCC patients with brain metastasis, I+N is clinically effective. Further investigation is warranted in this population given exclusion from prior clinical trials.

scholarly journals Predictive Role of Prior Radiotherapy and Immunotherapy-Related Adverse Effects in Advanced NSCLC Patients Receiving Anti-PD-1/L1 Therapy

2021 ◽  
Vol 10 (16) ◽  
pp. 3719
Author(s):  
Jeong Uk Lim ◽  
Soo Han Kim ◽  
Hye Seon Kang ◽  
Sung Kyoung Kim ◽  
Ju Sang Kim ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Asan Medical ◽  
Predictive Role ◽  
Independent Association ◽  
Nsclc Patients ◽  
The Impact

The present study evaluated the impact of prior radiotherapy (RT) on patients with advanced non-small cell lung cancer (NSCLC) receiving therapy with immune checkpoint inhibitors (ICIs) and further assessed the prognostic factors in patients receiving both RT and ICI. Patients diagnosed with NSCLC at the Catholic Medical Center and Asan Medical Center between January 2016 and October 2020 and who received immunotherapy were retrospectively reviewed. Among 240 patients, poor Eastern Cooperative Oncology Group (ECOG) score, high PD-L1 expression, and ICI-related adverse events (AE) were significantly associated with progression-free survival (PFS) (HR, 2.654; 95% CI, 1.484–4.749; p = 0.001; HR, 0.645; 95% CI, 0.449–0.926, p = 0.017; HR, 0.430; 95% CI, 0.229–0.808; p = 0.009, respectively). Among patients who received both RT and immunotherapy, poor ECOG status, squamous cell carcinoma, and ICI-related AE were significant factors associated with poor PFS (HR, 2.430; 95% CI, 1.464–4.034; p = 0.001; HR, 0.667; 95% CI, 0.455–0.978, p = 0.038; HR, 0.520; 95% CI, 0.284–0.953, p = 0.034, respectively). The present study showed that prior RT showed no significant independent association with primary outcomes in patients with advanced NSCLC receiving immunotherapy. In patients who received both RT and immunotherapy, clinical parameters, including ICI-related AEs, were independently predictive of PFS.

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