22 research outputs found
Family history of cancer, personal history of medical conditions and risk of oral cavity cancer in France: the ICARE study
Single or combined immune checkpoint inhibitors compared to firstâline platinumâbased chemotherapy with or without bevacizumab for people with advanced nonâsmall cell lung cancer
Background
Immune checkpoint inhibitors (ICIs) targeting the PDâ1/PDâL1 axis have changed the firstâline treatment of people with advanced nonâsmall cell lung cancer (NSCLC). Singleâagent pembrolizumab (a PDâ1 inhibitor) is currently the standard of care as monotherapy in patients with PDâL1 expression â„ 50%, either alone or in combination with chemotherapy when PDâL1 expression is less than 50%. Atezolizumab (PDâL1 inhibitor) has also been approved in combination with chemotherapy and bevacizumab (an antiâangiogenic antibody) in firstâline NSCLC regardless of PDâL1 expression. The combination of firstâline PDâ1/PDâL1 inhibitors with antiâCTLAâ4 antibodies has also been shown to improve survival compared to platinumâbased chemotherapy in advanced NSCLC, particularly in people with high tumour mutational burden (TMB). The association of ipilimumab (an anti CTLA4) and nivolumab (PDâ1 inhibitor) has been approved by the US Food and Drug Administration (FDA) in all patients with PDâL1 expression â„1%. Although these antibodies are currently used in clinical practice, some questions remain unanswered, such as the bestâtreatment strategy, the role of different biomarkers for treatment selection and the effectiveness of immunotherapy according to specific clinical characteristics.
Objectives
Primary objective: to determine the effectiveness and safety of firstâline immune checkpoint inhibitors (ICIs), as monotherapy or in combination, compared to platinumâbased chemotherapy, with or without bevacizumab for people with advanced NSCLC, according to the level of PDâL1 expression. Secondary objective: to maintain the currency of evidence using a living systematic review approach.
Search methods
We performed an electronic search of the main databases (Cochrane Lung Cancer Group Trial Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase) from inception until 21 October 2020 and conferences meetings from 2015 onwards.
Selection criteria
We included randomised controlled trials (RCTs) reporting on the efficacy or safety of firstâline ICI treatment for adults with advanced NSCLC who had not previously received any anticancer treatment. We included trials comparing singleâ or doubleâICI treatment to standard firstâline therapy (platinumâbased chemotherapy +/â bevacizumab). All data come from âinternational multicentre studies involving adults, age 18 or over, with histologicallyâconfirmed stage IV NSCLC who had not received any previous systemic antiâcancer treatment for advanced disease.
Data collection and analysis
Three review authors independently assessed the search results and a fourth review author resolved any disagreements. Primary outcomes were overall survival (OS) and progressionâfree survival (PFS); secondary outcomes were overall objective response rate (ORR) by RECIST v 1.1, grade 3 to 5 treatmentârelated adverse events (AEs) (CTCAE v 5.0) and healthârelated quality of life (HRQoL). We performed metaâanalyses where appropriate using the randomâeffects model for hazard ratios (HRs) or risk ratios (RRs), with 95% confidence intervals (95% CIs), and used the IÂČ statistic to investigate heterogeneity.
Main results
Main results
We identified 15 trials for inclusion, seven completed and eight ongoing trials. We obtained data for 5893 participants from seven trials comparing firstâline singleâ (six trials) or doubleâ (two trials) agent ICI with platinumâbased chemotherapy, one trial comparing both firstâline singleâ and doubleâagent ICsI with platinumâbased chemotherapy. All trials were at low risk of selection and detection bias, some were classified at high risk of performance, attrition or other source of bias. The overall certainty of evidence according to GRADE ranged from moderateâtoâlow because of risk of bias, inconsistency, or imprecision. The majority of the included trials reported their outcomes by PDâL1 expressions, with PDâL1 â„ 50 being considered the most clinically useful cutâoff level for decision makers. Also, iIn order to avoid overlaps between various PDLâ1 expressions we prioritised the review outcomes according to PDâL1 â„ 50.
Singleâagent ICI
In the PDâL1 expression â„ 50% group singleâagent ICI probably improved OS compared to platinumâbased chemotherapy (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.60 to 0.76, 6 RCTs, 2111 participants, moderateâcertainty evidence). In this group, singleâagent ICI also may improve PFS (HR: 0.68, 95% CI 0.52 to 0.88, 5 RCTs, 1886 participants, lowâcertainty evidence) and ORR (risk ratio (RR):1.40, 95% CI 1.12 to 1.75, 4 RCTs, 1672 participants, lowâcertainty evidence). HRQoL data were available for only one study including only people with PDâL1 expression â„ 50%, which suggested that singleâagent ICI may improve HRQoL at 15 weeks compared to platinumâbased chemotherapy (RR: 1.51, 95% CI 1.08 to 2.10, 1 RCT, 297 participants, lowâcertainty evidence).
In the included studies, treatmentârelated AEs were not reported according to PDâL1 expression levels. Grade 3â4 AEs may be less frequent with singleâagent ICI compared to platinumâbased chemotherapy (RR: 0.41, 95% CI 0.33 to 0.50, IÂČ = 62%, 5 RCTs, 3346 participants, lowâcertainty evidence).
More information about efficacy of singleâagent ICI compared to platinumâbased chemotherapy according to the level of PDâL1 expression and to TMB status or specific clinical characteristics is available in the full text.
Doubleâagent ICI
DoubleâICI treatment probably prolonged OS compared to platinumâbased chemotherapy in people with PDâL1 expression â„50% (HR: 0.72, 95% CI 0.59 to 0.89 2 RCTs, 612 participants, moderateâcertainty evidence).
Trials did not report data on HRQoL, PFS and ORR according to PDâL1 groups.
Treatment related AEs were not reported according to PDâL1 expression levels. The frequency of grade 3â4 AEs may not differ between doubleâICI treatment and platinumâbased chemotherapy (RR: 0.78, 95% CI 0.55 to 1.09, IÂČ = 81%, 2 RCTs, 1869 participants, lowâcertainty evidence).
More information about efficacy of doubleâagent ICI according to the level of PDâL1 expression and to TMB status is available in the full text.
Authors' conclusions
Authors' conclusions
The evidence in this review suggests that singleâagent ICI in people with NSCLC and PDâL1 â„50% probably leads to a higher overall survival rate and may lead to a higher progressionâfree survival and overall response rate when compared to platinumâbased chemotherapy and may also lead to a lower rate of adverse events and higher HRQoL. Combined ICI in people with NSCLC and PDâL1 â„50% also probably leads to a higher overall survival rate when compared to platinumâbased chemotherapy, but its effect on progressionâfree survival, overall response rate and HRQoL is unknown due to a lack of data. The rate of adverse events may not differ between groups.</p
Single or combined immune checkpoint inhibitors compared to firstâline platinumâbased chemotherapy with or without bevacizumab for people with advanced nonâsmall cell lung cancer
Background
Immune checkpoint inhibitors (ICIs) targeting the PDâ1/PDâL1 axis have changed the firstâline treatment of people with advanced nonâsmall cell lung cancer (NSCLC). Singleâagent pembrolizumab (a PDâ1 inhibitor) is currently the standard of care as monotherapy in patients with PDâL1 expression â„ 50%, either alone or in combination with chemotherapy when PDâL1 expression is less than 50%. Atezolizumab (PDâL1 inhibitor) has also been approved in combination with chemotherapy and bevacizumab (an antiâangiogenic antibody) in firstâline NSCLC regardless of PDâL1 expression. The combination of firstâline PDâ1/PDâL1 inhibitors with antiâCTLAâ4 antibodies has also been shown to improve survival compared to platinumâbased chemotherapy in advanced NSCLC, particularly in people with high tumour mutational burden (TMB). The association of ipilimumab (an anti CTLA4) and nivolumab (PDâ1 inhibitor) has been approved by the US Food and Drug Administration (FDA) in all patients with PDâL1 expression â„1%. Although these antibodies are currently used in clinical practice, some questions remain unanswered, such as the bestâtreatment strategy, the role of different biomarkers for treatment selection and the effectiveness of immunotherapy according to specific clinical characteristics.
Objectives
To determine the effectiveness and safety of firstâline immune checkpoint inhibitors (ICIs), as monotherapy or in combination, compared to platinumâbased chemotherapy, with or without bevacizumab for people with advanced NSCLC, according to the level of PDâL1 expression.
Search methods
We performed an electronic search of the main databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase) from inception until 31 December 2020 and conferences meetings from 2015 onwards.
Selection criteria
We included randomised controlled trials (RCTs) reporting on the efficacy or safety of firstâline ICI treatment for adults with advanced NSCLC who had not previously received any anticancer treatment. We included trials comparing singleâ or doubleâICI treatment to standard firstâline therapy (platinumâbased chemotherapy +/â bevacizumab). All data come from âinternational multicentre studies involving adults, age 18 or over, with histologicallyâconfirmed stage IV NSCLC.
Data collection and analysis
Three review authors independently assessed the search results and a fourth review author resolved any disagreements. Primary outcomes were overall survival (OS) and progressionâfree survival (PFS); secondary outcomes were overall objective response rate (ORR) by RECIST v 1.1, grade 3 to 5 treatmentârelated adverse events (AEs) (CTCAE v 5.0) and healthârelated quality of life (HRQoL). We performed metaâanalyses where appropriate using the randomâeffects model for hazard ratios (HRs) or risk ratios (RRs), with 95% confidence intervals (95% CIs), and used the IÂČ statistic to investigate heterogeneity.
Main results
Main results
We identified 15 trials for inclusion, seven completed and eight ongoing trials. We obtained data for 5893 participants from seven trials comparing firstâline singleâ (six trials) or doubleâ (two trials) agent ICI with platinumâbased chemotherapy, one trial comparing both firstâline singleâ and doubleâagent ICsI with platinumâbased chemotherapy. All trials were at low risk of selection and detection bias, some were classified at high risk of performance, attrition or other source of bias. The overall certainty of evidence according to GRADE ranged from moderateâtoâlow because of risk of bias, inconsistency, or imprecision. The majority of the included trials reported their outcomes by PDâL1 expressions, with PDâL1 â„ 50 being considered the most clinically useful cutâoff level for decision makers. Also, iIn order to avoid overlaps between various PDLâ1 expressions we prioritised the review outcomes according to PDâL1 â„ 50.
Singleâagent ICI
In the PDâL1 expression â„ 50% group singleâagent ICI probably improved OS compared to platinumâbased chemotherapy (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.60 to 0.76, 6 RCTs, 2111 participants, moderateâcertainty evidence). In this group, singleâagent ICI also may improve PFS (HR: 0.68, 95% CI 0.52 to 0.88, 5 RCTs, 1886 participants, lowâcertainty evidence) and ORR (risk ratio (RR):1.40, 95% CI 1.12 to 1.75, 4 RCTs, 1672 participants, lowâcertainty evidence). HRQoL data were available for only one study including only people with PDâL1 expression â„ 50%, which suggested that singleâagent ICI may improve HRQoL at 15 weeks compared to platinumâbased chemotherapy (RR: 1.51, 95% CI 1.08 to 2.10, 1 RCT, 297 participants, lowâcertainty evidence).
In the included studies, treatmentârelated AEs were not reported according to PDâL1 expression levels. Grade 3â4 AEs may be less frequent with singleâagent ICI compared to platinumâbased chemotherapy (RR: 0.41, 95% CI 0.33 to 0.50, IÂČ = 62%, 5 RCTs, 3346 participants, lowâcertainty evidence).
More information about efficacy of singleâagent ICI compared to platinumâbased chemotherapy according to the level of PDâL1 expression and to TMB status or specific clinical characteristics is available in the full text.
Doubleâagent ICI
DoubleâICI treatment probably prolonged OS compared to platinumâbased chemotherapy in people with PDâL1 expression â„50% (HR: 0.72, 95% CI 0.59 to 0.89 2 RCTs, 612 participants, moderateâcertainty evidence).
Trials did not report data on HRQoL, PFS and ORR according to PDâL1 groups.
Treatment related AEs were not reported according to PDâL1 expression levels. The frequency of grade 3â4 AEs may not differ between doubleâICI treatment and platinumâbased chemotherapy (RR: 0.78, 95% CI 0.55 to 1.09, IÂČ = 81%, 2 RCTs, 1869 participants, lowâcertainty evidence).
More information about efficacy of doubleâagent ICI according to the level of PDâL1 expression and to TMB status is available in the full text.
Authors' conclusions
Authors' conclusions
The evidence in this review suggests that singleâagent ICI in people with NSCLC and PDâL1 â„50% probably leads to a higher overall survival rate and may lead to a higher progressionâfree survival and overall response rate when compared to platinumâbased chemotherapy and may also lead to a lower rate of adverse events and higher HRQoL. Combined ICI in people with NSCLC and PDâL1 â„50% also probably leads to a higher overall survival rate when compared to platinumâbased chemotherapy, but its effect on progressionâfree survival, overall response rate and HRQoL is unknown due to a lack of data. The rate of adverse events may not differ between groups.
This review used to be a living review. It is transitioned out of living mode because current research is exploring ICI in association with chemotherapy or other immunotherapeutic drugs versus ICI as single agent rather than platinum based chemotherapy.</p
Occupational exposure to petroleum-based and oxygenated solvents and hypopharyngeal and laryngeal cancer in France the ICARE study
International audienceBACKGROUND:To examine associations between occupational exposure to petroleum-based and oxygenated solvents and the risk of hypopharyngeal and laryngeal cancer.METHODS:ICARE is a large, frequency-matched population-based case-control study conducted in France. Lifetime occupational history, tobacco smoking and alcohol consumption were collected. Analyses were restricted to men and included 383 cases of hypopharyngeal cancer, 454 cases of laryngeal cancer, and 2780 controls. Job-exposure matrices were used to assess exposure to five petroleum-based solvents (benzene; gasoline; white spirits; diesel, fuels and kerosene; special petroleum products) and to five oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). Odds ratios (ORs) adjusted for smoking, alcohol drinking and other potential confounders and 95% confidence intervals (CI) were estimated with unconditional logistic models.RESULTS:No significant association was found between hypopharyngeal or laryngeal cancer risk and exposure to the solvents under study. Non-significantly elevated risks of hypopharyngeal cancer were found in men exposed to high cumulative levels of white spirits (ORâ=â1.46; 95% CI: 0.88-2.43) and tetrahydrofuran (ORâ=â2.63; 95CI%: 0.55-12.65), with some indication of a dose-response relationship (p for trend: 0.09 and 0.07 respectively).CONCLUSION:This study provides weak evidence for an association between hypopharyngeal cancer and exposure to white spirits and tetrahydrofuran, and overall does not suggest a substantial role of exposure to petroleum-based or oxygenated solvents in hypopharyngeal or laryngeal cancer risk
Occupational exposure to petroleum-based and oxygenated solvents and hypopharyngeal and laryngeal cancer in France: the ICARE study
Systematic screening for occupations and occupational exposures in head and neck squamous cell carcinoma patients
A case of laryngeal cancer induced by exposure to asbestos in a construction site supervisor
Evaluation of miR 31 3p as a biomarker of prognosis and panitumumab benefit in RAS-wt advanced colorectal cancer (aCRC): Analysis of patients (pts) from the PICCOLO trial
Occupational exposure to chlorinated solvents and risk of head and neck cancer in men: a population-based case-control study in France
Prognostic nomogram and score to predict overall survival in locally advanced untreated pancreatic cancer (PROLAP)
Background: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP). Methods: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besançon Hospital, France. Results: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index=0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P<0.0001). The score ability to discriminate OS was externally confirmed in 63 (59%) patients with complete clinical data derived from a data set of 106 consecutive LAPC patients; median OS of 18.3, 14.1 and 7.6 months for the three groups (log-rank P<0.0001). Conclusions: The PROLAP nomogram and score can accurately predict OS before initiation of induction chemotherapy in LAPC-untreated patients. They may help to optimise clinical trials design and might offer the opportunity to define risk-Adapted strategies for LAPC management in the future