The phase 3 PACIFIC trial established consolidation therapy with durvalumab as standard of care for patients with unresectable, stage III NSCLC and no disease progression after definitive ...chemoradiotherapy (CRT). The observational PACIFIC-R study assesses the real-world effectiveness of durvalumab in patients from an early access program. Here, we report treatment characteristics and a preplanned analysis of real-world progression-free survival (rwPFS).
PACIFIC-R (NCT03798535) is an ongoing, international, retrospective study of patients who started durvalumab (intravenously; 10 mg/kg every 2 wk) within an early access program between September 2017 and December 2018. The primary end points are investigator-assessed rwPFS and overall survival (analyzed by Kaplan–Meier method).
As of November 30, 2020, the full analysis set comprised 1399 patients from 11 countries (median follow-up duration, 23.5 mo). Patients received durvalumab for a median of 11.0 months. Median rwPFS was 21.7 months (95% confidence interval: 19.1–24.5). RwPFS was numerically longer among patients who received concurrent versus sequential CRT (median, 23.7 versus 19.3 mo) and among patients with programmed cell death-ligand 1 expression greater than or equal to 1% versus less than 1% (22.4 versus 15.6 mo). Overall, 16.5% of the patients had adverse events leading to treatment discontinuation; 9.5% of all patients discontinued because of pneumonitis or interstitial lung disease.
Consolidation durvalumab after definitive CRT was well tolerated and effective in this large, real-world cohort study of patients with unresectable, stage III NSCLC. As expected, rwPFS was longer among patients who received concurrent versus sequential CRT and patients with higher programmed cell death-ligand 1 expression. Nevertheless, favorable rwPFS outcomes were observed regardless of these factors.
Eosinophils and Lung Cancer: From Bench to Bedside Sibille, Anne; Corhay, Jean-Louis; Louis, Renaud ...
International journal of molecular sciences,
05/2022, Volume:
23, Issue:
9
Journal Article, Web Resource
Peer reviewed
Open access
Eosinophils are rare, multifunctional granulocytes. Their growth, survival, and tissue migration mainly depend on interleukin (IL)-5 in physiological conditions and on IL-5 and IL-33 in inflammatory ...conditions. Preclinical evidence supports an immunological role for eosinophils as innate immune cells and as agents of the adaptive immune response. In addition to these data, several reports show a link between the outcomes of patients treated with immune checkpoint inhibitors (ICI) for advanced cancers and blood eosinophilia. In this review, we present, in the context of non-small cell lung cancer (NSCLC), the biological properties of eosinophils and their roles in homeostatic and pathological conditions, with a focus on their pro- and anti-tumorigenic effects. We examine the possible explanations for blood eosinophilia during NSCLC treatment with ICI. In particular, we discuss the value of eosinophils as a potential prognostic and predictive biomarker, highlighting the need for stronger clinical data. Finally, we conclude with perspectives on clinical and translational research topics on this subject.
To contribute to a precise and thorough knowledge of immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) and to emphasize the importance of this specific form of ...toxicity in terms of potential predictive value and long-term effects.
We report the first case of granulomatosis with polyangiitis (GPA) in a patient treated with an anti-Programmed Death protein-1 (PD-1) antibody for advanced non-small-cell lung cancer (NSCLC).
After a single dose of this drug the patient showed severe myositis associated with a high anti-PR3 anti-neutrophil cytoplasmic antibody titer. Discontinuation of the anti-PD-1 and introduction of corticoids led to a remission of the irAE. Regarding tumor a partial response was noted. A year later a neutrophilic, sterile pleural exudate and cutaneous lesions appeared with the pathological findings of neutrophilic vasculitis. Retreatment with corticoids induced a new remission of symptoms. It remains unclear whether GPA was preexisting and clinically silent but revealed by the use of ICI or primarily induced by this treatment. Conclusions: irAE are rare when anti-PD-1 antibodies are used in monotherapy. They present with a distinct clinical picture and temporal course and require specific treatment. Patients with irAE usually have a favorable oncological outcome.
The aim of our study was to determine the potential role of CT-based radiomics in predicting treatment response and survival in patients with advanced NSCLC treated with immune checkpoint inhibitors. ...We retrospectively included 188 patients with NSCLC treated with PD-1/PD-L1 inhibitors from two independent centers. Radiomics analysis was performed on pre-treatment contrast-enhanced CT. A delta-radiomics analysis was also conducted on a subset of 160 patients who underwent a follow-up contrast-enhanced CT after 2 to 4 treatment cycles. Linear and random forest (RF) models were tested to predict response at 6 months and overall survival. Models based on clinical parameters only and combined clinical and radiomics models were also tested and compared to the radiomics and delta-radiomics models. The RF delta-radiomics model showed the best performance for response prediction with an AUC of 0.8 (95% CI: 0.65-0.95) on the external test dataset. The Cox regression delta-radiomics model was the most accurate at predicting survival with a concordance index of 0.68 (95% CI: 0.56-0.80) (
= 0.02). The baseline CT radiomics signatures did not show any significant results for treatment response prediction or survival. In conclusion, our results demonstrated the ability of a CT-based delta-radiomics signature to identify early on patients with NSCLC who were more likely to benefit from immunotherapy.
Background
The spread of the COVID‐19 pandemic has led to a rapid reorganization in all human and hospital activities, with impact on cancer patients.
Aim
An analysis of cancer patients fears, and ...awareness of COVID‐19 has been done in this study.
Methods and results
We analyzed cancer patients' reactions to the pandemic and their perception of oncological care reorganization, through a 12‐item survey, proposed at the peak of pandemic and 3 months later. Overall, 237 patients were included in the study. During the peak of pandemic 34.6% of patients were more worried about COVID‐19 than cancer versus 26.4% in the post‐acute phase (p = .013). Although 49.8% of patients in the acute phase and 42.3% in the post‐acute phase considered their risk of death if infected ≥50%, and more than 70% of patients thought to be at higher risk of complications, the majority of them did not consider the possibility to stop or delay their treatment. Patients were more interested in following news about COVID‐19 than cancer and they complied with all preventive measures in more than 90% of the cases.
Conclusions
Although cancer patients worried about COVID‐19 and evaluated the risk of complication or death due to COVID‐19 as extremely high, they were still asking for the best oncological treatment.
IntroductionFucosyl-GM1 is a monosialoganglioside with limited expression in healthy tissues and high expression on SCLC cells. BMS-986012 is a nonfucosylated, first-in-class, fully human ...immunoglobulin G1 monoclonal antibody that binds to fucosyl-GM1. MethodsCA001-030 is a phase 1/2, first-in-human study of BMS-986012 as monotherapy or in combination with nivolumab for adults with relapsed or refractory SCLC. Safety is the primary end point. Additional end points include objective response rate, duration of response, progression-free survival, pharmacokinetics, and overall survival. ResultsPatients (BMS-986012 monotherapy, n = 77; BMS-986012 + nivolumab, n = 29) were predominantly of male sex (58%), 63 years old (mean), current or past tobacco users (97%), and treated previously with first-line systemic therapy (99%). The most common treatment-related adverse event was pruritus (n = 95 90%). Grade 4 treatment-related adverse events were reported in 2% (n = 2) of patients. The objective response rate (95% confidence interval CI) was higher with BMS-986012 plus nivolumab (38% 20.7%-57.7%) than with monotherapy (4% 0.8%-11.0%). Median (95% CI) duration of response with BMS-986012 plus nivolumab was 26.4 (4.4-not reached) months. Progression-free survival (95% CI) at 24 weeks with monotherapy and BMS-986012 plus nivolumab was 12.2% (6.0%-20.7%) and 39.3% (21.7%-56.5%), respectively. The pharmacokinetics profile of monotherapy and BMS-986012 plus nivolumab suggested dose proportionality across the tested dose range. Median overall survival (95% CI) with monotherapy and BMS-986012 plus nivolumab was 5.4 (4.0-7.3) and 18.7 (8.2-37.3) months, respectively. ConclusionsBMS-986012 in combination with nivolumab represents a well-tolerated, potential new therapy for relapsed or refractory SCLC. BMS-986012 is currently being explored in combination with carboplatin, etoposide, and nivolumab as a first-line therapy in extensive-stage SCLC (NCT04702880).
This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naïve, extensive-stage small cell lung cancer (ED-SCLC).
...Patients were randomized 1:1:1 to veliparib 240 mg twice daily (BID) for 14 days plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control.
Overall (
= 181), PFS was improved with veliparib throughout versus control hazard ratio (HR), 0.67; 80% confidence interval (CI), 0.50-0.88;
= 0.059; median PFS was 5.8 and 5.6 months, respectively. There was a trend toward improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR, 0.6; 80% CI, 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR, 1.43; 80% CI, 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, veliparib combination-only and control arms, most commonly hematologic.
Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting.
Abstract only
e15542
Background: Lung cancer diagnosis relies on invasive methods and often occurs at a late stage of disease, explaining its poor outcome. Nucleosomes are DNA fragments wrapped ...around histones. They may constitute a non-invasive and early diagnostic method for lung cancer. We investigated the clinical and statistical performance of nucleosome assay levels alone and in combination with cytokines in plasma from untreated lung cancer (LC) patients and what their discriminant power was towards chronic obstructive pulmonary disease (COPD) and healthy (H) subjects. Methods: 142 plasma samples were prospectively collected: H, n = 45; LC, n = 44 and COPD, n = 53. The circulating level of intact nucleosomes containing the histone H3.1 isoform (Nu.Qª-H3.1) was individually tested and in combination with cytokines for its performance in discriminating subjects for their underlying condition. Then, statistical performance of each model was tested with binary logistic regression models for the best combination of biomarkers for the following groups: cancer vs control (group A), cancer vs COPD+control (group B) and for cancer vs COPD (group C). The best model for each group was then applied to two independent biobank cohorts for validation. Results: Results for Nu.Q-H3.1 was an area under the curve (AUC) of 0.79, for group A, B and C; a sensitivity of 68%, 66% and 66% for group A, B and C, respectively, for 80% specificity. For group A the H3.1+IL-10 model achieved a sensitivity of 77% for 80% specificity with an AUC of 0.88 (R² = 55.8%). For group B the H3.1+IL-6+IL-10 model achieved a sensitivity of 70% with an AUC of 0.85 (R² = 40.6%). For group C the H3.1+IL-6+IL-10 model achieved a sensitivity of 79% with an AUC of 0.85 (R² = 46.1%). The validation cohort performed similarly. Results for the 3 cohorts taken together were: AUC of 0.83, 0.87 and 0.90 for group A, B and C, respectively; sensitivity of 75%, 76 % and 84% for group A, B and C, respectively, for 80% specificity. Conclusions: Nucleosomes are detected in the plasma of H, LC and COPD patients. Combination with cytokines as described in these models allows for a good power ofdiscrimination between the three groups. Based on these encouraging results, we believe further studies with larger numbers of patients should be performed to confirm and validate the usefulness of these biomarkers and models.
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