951 Immune Checkpoint Inhibitors-Related Gastrointestinal Toxicity Is Associated With Better Overall Survival and Treatment Response in Cancer Patients

ObjectivesImmune checkpoint inhibitors (ICIs) have brought impressive benefits to cancer patients, however often accompanied with immune-related adverse events (irAEs). We aimed to investigate the association of irAEs with efficacy and overall survival in cancer patients treated by ICIs, and further quantify the association by stratifying subgroups.MethodsPubMed, EMBASE and Cochrane library from database inception to 29 August 2019 were systematically searched. Articles reporting association of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) with irAEs in cancer patients treated with approved ICIs were included. Adjusted odds ratios (OR) with 95% confidential intervals (CIs) were calculated for ORR, and hazard ratios (HR) were used for PFS and OS.ResultsA total of 52 articles comprising 9,156 patients were included. Pooled data demonstrated a statistically significant greater probability of achieving objective tumor response for patients with irAEs compared to those without (OR 3.91, 95% CI 3.05–5.02). In overall meta-analysis, patients who developed irAEs presented a prolonged PFS (HR 0.54; 95% CI 0.46–0.62) and OS (HR 0.51; 95% CI 0.41–0.59). More specifically, irAEs in certain cancer types (NSCLC and melanoma) and organs (skin and endocrine) were robustly associated with better clinical outcomes, while this association needs further verification regarding other tumors. High grade toxicities (G3–5) were not associated with a significantly favorable PFS or OS. Additionally, the association between irAEs and clinical benefit seemed to be more definite in patients receiving PD-(L)1 blockade than CTLA-4 blockade. Pooled data from landmark analyses displayed consistent results.ConclusionsThe occurrence of irAEs predicted improved tumor response and better survival in overall cancer patients treated with ICIs. Notably, the association stayed robust in certain cancer types (NSCLC and melanoma) and organ-specific irAEs (skin and endocrine).

Download Full-text

The Effectiveness and Safety of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients With Stage III/IV: A Multicenter Study

Frontiers in Oncology ◽

10.3389/fonc.2021.671127 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jason C. Hsu ◽

Phung-Anh Nguyen ◽

Yen-Tzu Chen ◽

Szu-Chun Yang ◽

Chien-Chung Lin ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Adverse Drug Events ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancer Patients

Immune checkpoint inhibitors (ICIs) have been approved to treat patients with various cancer types, including lung cancer, in many countries. This study aims to investigate the effectiveness and safety of ICIs under different treatment conditions of non-small cell lung cancer patients. A population-based retrospective cohort study was conducted using the electronic health records of three medical centers in Taiwan. From January 01, 2016, to November 30, 2018, a total of 91 ICIs and 300 traditional chemotherapy users who had undergone stage III and IV lung cancer treatment were included in the study. We performed the randomized matched pair design by selecting a Chemotherapy subject for each ICI patient in the sample population. All subjects were monitored from the date of taking ICIs or chemotherapy drugs until the event of death, loss to follow-up, or were occurred with any defined adverse events. Kaplan-Meier estimators and cox proportional hazard regression models were used to compute the overall survival, efficacy, and safety of the ICIs group. The median overall survival (OS) in the ICI and Chemo groups after matching was 11.2 months and 10.5 months, respectively. However, the results showed no significant OS differences between ICIs and chemo groups for both before and after matching (HR,1.30; 95%CI, 0.68-2.46; p=0.428 before matching and HR,0.96; 95CI%, 0.64-1.44; p=0.838 after matching). We observed that with the higher amount of PD-L1, the length of the patients’ overall survival was (positive vs. negative PD-L1, HR,0.21; 95%CI, 0.05-0.80; p=0.022). The incidences of serious adverse drug events above grade 3 in the ICIs and traditional chemo groups were 12.7% and 21.5%, respectively. We also found that the number of AEs was less in ICIs than in the Chemo group, and the AEs that occurred after treatments were observed earlier in the ICIs compared to the Chemo group. ICIs drugs were observed to be safer than traditional chemotherapy as they had a lower risk of serious adverse drug events. It is necessary to pay attention to immune-related side effects and provide appropriate treatment. Furthermore, the patient’s physical status and PD-L1 test can be used to evaluate the clinical effectiveness of ICIs.

Download Full-text

Early changes in lymphocyte/monocyte ratio on-treatment as a prognostic marker to predict overall survival in patients with advanced cancer treated with immune checkpoint inhibitors

10.21203/rs.3.rs-758097/v1 ◽

2021 ◽

Author(s):

Sandip H. Patel ◽

Songzhu Zhao ◽

Mingjia Li ◽

Lai Wei ◽

Marium Husain ◽

...

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Advanced Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Predictive Biomarker ◽

Advanced Cancer Patients ◽

High Baseline

Abstract Background A low absolute lymphocyte/monocyte ratio (LMR) in the peripheral blood is associated with poor prognosis in various cancers; however, its role as a predictive biomarker has not been well defined in the era of treatment with immune checkpoint inhibitors (ICI). Methods We queried a database of advanced cancer patients treated with at least one dose of ICI from 2011 to 2017 to study the association of LMR with overall survival (OS). We calculated LMR at baseline and a median of 21 days after the first cycle of ICI (on-treatment LMR), and defined low if < 2 and high if ≥ 2. OS was calculated from the initiation of ICI to date of death or censored at last follow-up. Results 1077 patients met the criteria for this study. Patients with low baseline LMR had a shorter median OS compared to patients with a high baseline LMR (8.5 vs 18.1 months, p < 0.01). In patients with a low baseline LMR, who on-treatment LMR increased to high had longer median OS compared to those whose on-treatment LMR remained low (16.8 vs 7.8 months, p < 0.001). Patients with a high baseline LMR and in whom on-treatment LMR remained high had longer median OS compared to patients with low on-treatment LMR (23.9 vs 9.2 months, p < 0.001). In multivariate analysis, high on-treatment LMR was most strongly associated with longer survival compared to low on-treatment LMR, regardless of baseline LMR. Conclusions Higher baseline and early changes in on-treatment LMR are associated with improved OS in cancer patients receiving ICI.

Download Full-text

Randomized phase III trial on niraparib-TSR-042 (dostarlimab) versus physician’s choice chemotherapy in recurrent ovarian, fallopian tube, or primary peritoneal cancer patients not candidate for platinum retreatment: NItCHE trial (MITO 33)

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002593 ◽

2021 ◽

Vol 31 (10) ◽

pp. 1369-1373

Author(s):

Lucia Musacchio ◽

Vanda Salutari ◽

Sandro Pignata ◽

Elena Braicu ◽

David Cibula ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Recurrent Ovarian Cancer ◽

Primary Objective ◽

Phase Iii ◽

Polymerase Inhibitors

BackgroundPlatinum-resistant ovarian cancer patients have a poor prognosis and few treatment options are available. Preclinical and clinical data demonstrated that the combination of poly-ADP ribose polymerase inhibitors with immune checkpoint inhibitors could have a synergistic antitumor activity in this setting of patients.Primary ObjectiveThe primary objective is to assess the efficacy of niraparib plus dostarlimab compared with chemotherapy in recurrent ovarian cancer patients not suitable for platinum treatment.Study HypothesisThis trial will assess the hypothesis that niraparib plus dostarlimab therapy is effective to increase overall survival, progression-free survival, and time to first subsequent therapy respect to chemotherapy alone, with an acceptable toxicity profile.Trial DesignThis is a phase III, multicenter trial, where recurrent ovarian cancer patients not eligible for platinum re-treatment will be randomized 1:1 to receive niraparib plus dostarlimab vs physician’s choice chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent. The study will be performed according to European Network for Gynaecological Oncological Trial groups (ENGOT) model B and patients will be recruited from 40 sites across MITO, CEEGOG, GINECO, HeCOG, MANGO, and NOGGO groups.Major Inclusion/Exclusion criteriaEligible patients must have recurrent epithelial ovarian cancer not eligible for platinum retreatment. Patients who received previous treatment with poly-ADP ribose polymerase inhibitors and/or immune checkpoint inhibitors will be eligible. No more than two prior lines of treatment are allowed.Primary EndpointThe primary endpoint is overall survival defined as the time from the randomization to the date of death by any cause.Sample Size427 patients will be randomized.Estimated Dates for Completing Accrual and Presenting ResultsJune 2024Trial Registration NumberNCT04679064.

Download Full-text