Outcomes after retreatment with MAPK inhibitors and immune checkpoint inhibitors in melanoma patients

Advanced Melanoma ◽

Disease Control Rate ◽

Unknown Primary ◽

Free Survival ◽

Mapk Inhibitors

Background: When patients with advanced melanoma progress after MAPK inhibitor (MAPKI) and immune checkpoint inhibitor (ICI) treatment, they can either undergo chemotherapy or rechallenge with previously used treatments. Methods: The outcomes of 48 patients retreated with MAPKIs and 50 patients retreated with ICIs following progression were retrospectively analyzed. Results: Upon retreatment with MAPKIs, the disease control rate was 60%. Univariate analysis of possible risk factors associated with short progression-free survival upon MAPKI treatment showed elevated lactate dehydrogenase to be associated with decreased progression-free survival. Disease control rate after ICI retreatment was 24%. Melanoma of unknown primary was associated with prolonged progression-free survival upon ICI retreatment. Conclusion: Retreatment with MAPKIs or ICIs is a feasible option for patients with advanced melanoma.

Molecular profiling of advanced malignancies guides first-line N-of-1 treatments in the I-PREDICT treatment-naïve study

Genome Medicine ◽

10.1186/s13073-021-00969-w ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Jason K. Sicklick ◽

Shumei Kato ◽

Ryosuke Okamura ◽

Hitendra Patel ◽

Mina Nikanjam ◽

...

Keyword(s):

Disease Control ◽

Complete Response ◽

Disease Control Rate ◽

Unknown Primary ◽

Combination Therapies ◽

First Line ◽

Free Survival ◽

Treatment Naïve ◽

Matching Score

Abstract Background Malignancies are molecularly complex and become more resistant with each line of therapy. We hypothesized that offering matched, individualized combination therapies to patients with treatment-naïve, advanced cancers would be feasible and efficacious. Patients with newly diagnosed unresectable/metastatic, poor-prognosis cancers were enrolled in a cross-institutional prospective study. Methods A total of 145 patients were included in the study. Genomic profiling (tissue and/or circulating tumor DNA) was performed in all patients, and PD-L1 immunohistochemistry, tumor mutational burden, and microsatellite status assessment were performed in a subset of patients. We evaluated safety and outcomes: disease-control rate (stable disease for ≥ 6 months or partial or complete response), progression-free survival (PFS), and overall survival (OS). Results Seventy-six of 145 patients (52%) were treated, most commonly for non-colorectal gastrointestinal cancers, carcinomas of unknown primary, and hepatobiliary malignancies (53% women; median age, 63 years). The median number of deleterious genomic alterations per patient was 5 (range, 0–15). Fifty-four treated patients (71%) received ≥ 1 molecularly matched therapy, demonstrating the feasibility of administering molecularly matched therapy. The Matching Score, which reflects the percentage of targeted alterations, correlated linearly with progression-free survival (R2 = 0.92; P = 0.01), and high (≥ 60%) Matching Score was an independent predictor of improved disease control rate [OR 3.31 (95% CI 1.01–10.83), P = 0.048], PFS [HR 0.55 (0.28–1.07), P = 0.08], and OS [HR 0.42 (0.21–0.85), P = 0.02]. Serious adverse event rates were similar in the unmatched and matched groups. Conclusions Personalized combination therapies targeting a majority of a patient’s molecular alterations have antitumor activity as first-line treatment. These findings underscore the feasibility and importance of using tailored N-of-1 combination therapies early in the course of lethal malignancies. Trial registration I-PREDICT (NCT02534675) was registered on August 25, 2015.

Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors

OncoImmunology ◽

10.1080/2162402x.2019.1568812 ◽

2019 ◽

Vol 8 (4) ◽

pp. e1568812 ◽

Cited By ~ 54

Author(s):

Arielle Elkrief ◽

Layal El Raichani ◽

Corentin Richard ◽

Meriem Messaoudene ◽

Wiam Belkaid ◽

...

Keyword(s):

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Advanced Melanoma ◽

Free Survival ◽

Melanoma Patients

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

Cancer Biomarkers ◽

10.3233/cbm-210349 ◽

2021 ◽

pp. 1-11

Author(s):

Deniz Can Guven ◽

Oktay Halit Aktepe ◽

Melek Seren Aksun ◽

Taha Koray Sahin ◽

Gozde Kavgaci ◽

...

Keyword(s):

Immune Checkpoint ◽

Multivariate Analyses ◽

Checkpoint Inhibitors ◽

Free Survival ◽

Patients With Cancer ◽

Early Progression ◽

Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

Comparative Analysis of Durable Responses on Immune Checkpoint Inhibitors Versus Other Systemic Therapies: A Pooled Analysis of Phase III Trials

JCO Precision Oncology ◽

10.1200/po.18.00114 ◽

2019 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Elvire Pons-Tostivint ◽

Aurélien Latouche ◽

Pauline Vaflard ◽

Francesco Ricci ◽

Delphine Loirat ◽

...

Keyword(s):

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Phase Iii ◽

Durable Response ◽

Free Survival ◽

Drug Classes ◽

Metastatic Setting ◽

The Mean

PURPOSE Immune checkpoint inhibitors (ICIs) have been demonstrated to improve overall survival (OS) in several tumor types. Durable responses have been reported with these agents in patients with melanoma and lung cancer. We aimed to quantify the proportion of patients who experience durable responses on ICIs and to compare it with other drug classes. PATIENTS AND METHODS We retrieved published phase III randomized trials that included at least one ICI arm in the recurrent and/or metastatic setting. A durable response to treatment was defined as a progression-free survival that exceeded three times the median progression-free survival of the whole population. The proportion of patients who experienced an OS that exceeded two times the median OS of the whole patient population also was estimated. RESULTS Nineteen studies involving 11,640 patients treated in 42 treatment arms (26 ICI and 16 non-ICI arms) were included. The mean proportion of patients who experienced a durable response was 2.3 times higher in those treated with an ICI compared with those treated in the control arms (25% v 11%). Durable responses were more frequent in patients treated with anti–PD-1/PD-L1 agents than in patients treated with anti–CTLA-4 agents (28% v 18%). The mean proportion of patients who had an OS that exceeded two times the median OS was also higher in those treated with ICIs than in those treated in the control arms (30% v 23%). In multivariable analysis, the effects of treatment with anti–PD-1/PD-L1 agents and of first-line treatment were statistically associated with a higher mean proportion of durable responses. CONCLUSION Durable responses were more frequent in patients treated with ICIs, although they also occurred in patients treated with other drug classes.

Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors

10.1200/jco.19.03315 ◽

2020 ◽

Vol 38 (27) ◽

pp. 3088-3094 ◽

Cited By ~ 4

Author(s):

Anita Gul ◽

Tyler F. Stewart ◽

Charlene M. Mantia ◽

Neil J. Shah ◽

Emily Stern Gatof ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Immune Checkpoint ◽

Response Rate ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Free Survival ◽

Metastatic Rcc

PURPOSE Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS Patients with metastatic RCC who received prior anti–PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed. RESULTS Forty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients. CONCLUSION Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.

Efficacy of immune checkpoint inhibitors and age in cancer patients

Immunotherapy ◽

10.2217/imt-2019-0124 ◽

2020 ◽

Vol 12 (8) ◽

pp. 587-603 ◽

Cited By ~ 2

Author(s):

Xuan-zhang Huang ◽

Peng Gao ◽

Yong-xi Song ◽

Jing-xu Sun ◽

Xiao-wan Chen ◽

...

Keyword(s):

Cancer Patients ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Comparable Efficacy ◽

Control Groups ◽

Free Survival ◽

Meta Regression Analysis ◽

The Impact

Aim: To evaluate the impact of age on the efficacy of immune checkpoint inhibitors (ICI) in cancer patients. Materials & methods: The primary outcomes included overall survival (OS) and progression-free survival (PFS). Subgroup, meta-regression analysis and within-trial interaction HR were conducted. Results: A total of 34 studies containing 20,511 cancer patients were included. ICI could improve the OS and PFS in patient aged <65 and ≥65 years. Patients aged <75 years treated with ICI also had favorable OS and PFS compared with the control groups. Conclusion: ICI has comparable efficacy in cancer patients aged <65 and ≥65 years. Cancer patients aged ≥75 years need more attention in the future clinical trials.

Host metabolic factors and prognosis in patients treated with immune checkpoint inhibitors for advanced malignancies.

10.1200/jco.2019.37.15_suppl.e14162 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14162-e14162

Author(s):

Federica Biello ◽

Marco Audisio ◽

Silvia Genestroni ◽

Gloria Borra ◽

Francesca D'Avanzo ◽

...

Keyword(s):

Clinical Outcome ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Multivariable Analysis ◽

Fold Increase ◽

Advanced Melanoma ◽

Host Metabolism ◽

Increase In Risk

e14162 Background: It is well established that an altered host metabolism has an impact on cancer outcome, possibly mediated by several mechanisms, including hyperglicaemia, hyperinsulinemia and presence of chronic inflammation. The aim of our analysis was to evaluate the correlation between host metabolism and clinical outcome in patients with advanced melanoma, kidney and non-small cell lung cancer (NSCLC), treated with immune checkpoint inhibitors (anti-CTLA4, anti PD1 and anti PDL1). Methods: The relationship between presence of type 2 diabetes mellitus (DMII) at baseline and outcome was assessed in 187 patients treated with immune checkpoint inhibitors in two cancer centers. Progression Free Survival (PFS) and Overall Survival (OS) were calculated by Kaplan-Meier estimation; multivariate Cox analysis was performed according to age, gender, BMI (normal < 25 kg/m2, overweight 25-30 kg/m2, obese > 30 kg/m2), type of cancer and line of treatment. Results: One-hundred-sixty-eight patients were available for our analysis. Twenty-eight patients (17%) were diabetic at baseline. Median age was 65 (range 25-80); 83 patients were males (49%); 82 (48%) had advanced melanoma, 83 (49%) NSCLC and 3 (3%) kidney cancer. One-hundred-two (60%) patients had BMI < 25, 51 (30%) were overweight and 16 (10%) were obese. The first line of treatment was immunotherapy in 83 (49%) patients. By univariable analysis median PFS was 4.2 months in non diabetics vs 6.4 in diabetics patients (HR 0.95; 95%CI 0.58-1.58); median OS was 6.17 and 9.1 months, respectively (HR 1.00; 95%CI 0.58-1.75). At multivariable analysis, taking into account DMII, BMI, sex, age, line of treatment and type of cancer, we found that BMI ≤25 was associated with a two fold increase in risk of progression (PD) or death (p = 0.005), whereas patients who received immunotherapy as second or subsequent line had a two fold increase in risk of PD or death (p = 0.003). Conclusions: The results of our analysis show that in patients with advanced cancer treated with immune checkpoint inhibitors, the presence of DMII does not adversely affect the clinical outcome. Conversely, lower BMI was associated with a significantly worse PFS and OS, independently from type of cancer, age and gender. As expected, patients who received immunotherapy in later lines of treatment had a significantly shorter survival.

Efficacy of first-line immune checkpoint inhibitors in patients with sarcomatoid and/or rhabdoid (S/R) metastatic renal cell carcinoma (mRCC).

10.1200/jco.2019.37.8_suppl.66 ◽

2019 ◽

Vol 37 (8_suppl) ◽

pp. 66-66

Author(s):

Ziad Bakouny ◽

Sarah Abou Alaiwi ◽

Amin Nassar ◽

John A. Steinharter ◽

Xiao X. Wei ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Multivariable Analysis ◽

First Line ◽

Free Survival ◽

Logistic Regressions

66 Background: Patients with mRCC with S/R components tend to have a poor prognosis with few therapeutic options available. Recent data suggest that immune checkpoint inhibitor (ICI)-based therapies may be especially effective for these patients. Our aim was to evaluate the efficacy of ICI-based therapies in patients with S/R mRCC. Methods: We retrospectively assessed objective response rate (ORR), progression free survival (PFS) & overall survival (OS) of patients with S/R mRCC treated at our institution with first-line ICI-based therapies and compared these to those of patients treated with first-line non-ICI-based therapies. Univariable and multivariable (adjusted for IMDC group) Cox and logistic regressions were performed. Results: 92 patients (70 S, 9 R, and 13 S&R) patients were included, of which 74 with a clear-cell component. For all patients (regardless of therapy), 74 (80.4%) patients experienced a PFS event (progression or death) and 52 (56.5%) died at 25.3 months (m) median follow-up. Overall median PFS was 5.3 m (95% CI= 3.4–7.2) and 24 m OS rate was 39.5% (27.4–51.7). Out of 78 patients in whom response was evaluable, ORR was 30.8% (20.4–41.2). Patients treated with ICI-based therapies had significantly better ORR, PFS, and OS on multivariable analysis (table). Conclusions: mRCC patients with S/R components have significantly better ORR, PFS, and OS with first-line ICI-based compared to non-ICI-based therapies. These data support the use of ICI-based therapies for patients with S/R mRCC. [Table: see text]

Impact of baseline and concomitant corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy.

10.1200/jco.2020.38.4_suppl.531 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 531-531

Author(s):

David James Pinato ◽

Ahmed Omar Kaseb ◽

Yinghong Wang ◽

Anwaar Saeed ◽

David Szafron ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Evaluation Criteria ◽

Corticosteroid Treatment ◽

Free Survival ◽

Checkpoint Inhibitor Therapy ◽

The Impact

531 Background: The impact of corticosteroid treatment (CT) on the efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) is undefined. We evaluated whether CT administered at baseline (bCT) or concurrently to ICI (cCT) influences clinical outcomes of HCC patients treated with ICI. Methods: This retrospective, multi-center observational study was conducted across 9 tertiary academic referral centers collected 341 HCC patients who received ICI across 3 continents between January 1, 2016 and April 1, 2019. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of ICI commencement and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1) on 6-8 weekly periodic restaging. Results: Of 331 eligible patients, 254 (76%) had BCLC-C stage HCC and received mostly PD(L)-1 ICI monotherapy (n=250, 85%). Median OS was 12.1 months (95%CI 9.2-15.0 months) and median PFS was 8.1 months (95%CI 6.3-10 months). In total 81 patients (24%) received >10 mg prednisone equivalent daily either as bCT (n=15, 4%) or cCT (n=66, 20%). Indications for CT included procedure/prophylaxis (n=37, 45%), management of irAE (n=31, 37%), cancer-related symptoms (n=5, 2%) or comorbidities (n=8, 3%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in uni- and multi-variable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (2.4 vs. 11.3 months, p=0.01), OS (4.5 vs. 12.8 months, p=0.05) and reduced ORR (p=0.03) compared to cancer-unrelated indications. Conclusions: This is the first study to demonstrate that neither bCT nor cCT appear to influence response and OS following ICI in HCC. Worse survival and ORR in CT recipients for cancer-related indications appears driven by the poor prognosis associated with symptomatic HCC.

Inflammatory Markers Predict Survival in Patients With Advanced Gastric and Colorectal Cancers Receiving Anti–PD-1 Therapy

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.638312 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xiaona Fan ◽

Dan Wang ◽

Wenjing Zhang ◽

Jinshuang Liu ◽

Chao Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Disease Control ◽

Inflammatory Markers ◽

Overall Response Rate ◽

Response Rate ◽

Disease Control Rate ◽

Free Survival ◽

Lymphocyte Ratio

There is a lack of useful biomarkers for predicting the efficacy of anti–programmed death-1 (PD-1) therapy for advanced gastric and colorectal cancer. To address this issue, in this study we investigated the correlation between inflammatory marker expression and survival in patients with advanced gastric and colorectal cancer. Data for 111 patients with advanced gastric and colorectal cancer treated with anti–PD-1 regimens were retrospectively analyzed. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and clinical characteristics of each patient were selected as the main variables. Overall response rate, disease control rate, and progression-free survival were primary endpoints, and overall survival and immune-related adverse events (irAEs) were secondary endpoints. The chi-squared test and Fisher’s exact test were used to evaluate relationships between categorical variables. Uni- and multivariate Cox regression analyses were performed, and median progression-free survival and overall survival were estimated with the Kaplan–Meier method. The overall response rate and disease control rate of anti–PD-1therapy in advanced gastric and colorectal tumors were 12.61 and 66.66%, respectively. The patients with MLR < 0.31, NLR < 5, and PLR < 135 had a significantly higher disease control rate than those with MLR > 0.31, NLR > 5, and PLR > 135 (P < 0.05). The multivariate analysis revealed that MLR < 0.31, BMI > 18.5, and anti–PD-1 therapy in first-line were associated with prolonged PFS. MLR < 0.31 and BMI > 18.5 were associated with prolonged overall survival. The irAE rate differed significantly between PLR groups, and PLR < 135 was associated with an increased rate of irAEs (P = 0.028). These results indicate that the inflammatory markers NLR, MLR, and PLR have clinical utility for predicting survival or risk of irAEs in patients with advanced gastric cancer and colorectal cancer.