Immune checkpoint inhibitors plus chemotherapy versus chemotherapy or immunotherapy for first?line treatment of advanced non?small cell lung cancer: a generic protocol
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SUBMITTER: Syn N
PROVIDER: S-EPMC6494557 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
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Project description:BackgroundImmune-checkpoint inhibitors plus chemotherapy are emerging as effective first-line treatment in advanced non-small-cell lung carcinoma (NSCLC), but little is known about the magnitude of benefits and potential clinical predictors.MethodsWe performed a meta-analysis of randomized trials that compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy in first line of treatment for advanced NSCLC. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.ResultsSix trials involving 3144 patients were included. PD-1/PD-L1 inhibitor plus chemotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.62; 95% CI 0.57-0.67; P < .001), OS (HR, 0.68; 95% CI 0.53-0.87; P = .002) and ORR (relative ratio [RR], 1.56; 95% CI 1.29-1.89; P < .001), irrespective of PD-L1 expression level. The significant predictor(s) for treatment benefit with combination therapy versus chemotherapy alone were PD-L1 expression level for PFS (P < .001); types of checkpoint inhibitor for ORR (P < .001); histology (P = .025), age (P = .038), gender (P < .001), and types of checkpoint inhibitor (P < .001) for OS. In safety analyses, PD-1/PD-L1 inhibitor plus chemotherapy had significantly higher incidence of adverse events (AEs) of grade 3 or higher (RR, 1.14; P = .007), AEs leading to treatment discontinuation (RR, 1.29; P = .022), serious AEs (RR 1.70; P = .006), immune mediated AEs of any grade (RR, 2.37; P < .001), and immune mediated AEs of grade 3 or higher (RR, 3.71; P < .001).ConclusionsPD-1/PD-L1 inhibitor plus chemotherapy, compared with chemotherapy, is associated with significantly improved PFS, ORR, and OS in first-line therapy in NSCLC, at the expense of increased treatment-related AEs.
| S-EPMC6303974 | biostudies-literature
Project description:Immunotherapy has paved the way for new treatment options for advanced non-small cell lung cancer (NSCLC). However, for patients who have progressed following first-line immunotherapy combined with chemotherapy, little is known about the benefits of the continuation of immunotherapy. Thus, the current study aimed to evaluate the efficacy of immunotherapy beyond progression (IBP) in patients with advanced NSCLC. A retrospective review of patients with advanced NSCLC who experienced disease progression after receiving a combination of ICIs and chemotherapy was conducted. Kaplan-Meier survival analysis was used to estimate progression-free survival (PFS) and overall survival (OS) times, and log-rank tests were employed to compare inter-group differences. Cox regression analyses were performed to identify independent factors associated with OS and PFS. In total, 136 patients who had disease progression after prior immunotherapy were included. A comparison of patients who were treated with ICIs after disease progression (IBP group) and those who received other treatments (non-IBP group) demonstrated a higher disease control rate after second-line treatment for the IBP group (89.8 vs. 70.8%, respectively; P=0.005). Kaplan-Meier curve analysis showed statistical differences in PFS2 (interval from the second-line treatment to progression or death for any reason; P=0.012) and OS (P=0.041). Subgroup analyses indicated superior clinical outcomes for the IBP group. Multivariate analyses revealed IBP to be an independent factor associated with improved PFS2 (hazard ratio, 0.613; 95% confidence interval, 0.403-0.933; P=0.022). In conclusion, favorable clinical outcomes for IBP were observed, and IBP remains a viable choice for patients with advanced NSCLC.
| S-EPMC11638921 | biostudies-literature
Project description:ObjectiveThe KEYNOTE-590 trial showed that individuals with advanced esophageal cancer who received Pembrolizumab in combination with chemotherapy as a first-line regimen achieved a significant extension of survival. However, this treatment option increases the financial burden on patients and the economic benefits remain to be further evaluated.MethodsA Markov model was used to simulate 10-year survival of patients with esophageal cancer from the perspective of United States (US) Medicare payers. We evaluated the economics of Pembrolizumab plus chemotherapy in the PD-L1 positive score (CPS ≥10) and any PD-L1 expression groups, respectively. We estimated total costs, quality-adjusted life years (QALYs), and calculated incremental cost effectiveness ratios (ICERs). Sensitivity analyses were conducted to explore the impact of uncertainties on the results. Subgroup analysis was also performed.ResultsThe analysis results showed that the ICER for pembrolizumab plus chemotherapy versus chemotherapy alone was $293,513.17/QALYs in the any PD-L1 expression group. This exceeded the threshold of willingness to pay ($150,000/QALYs). ICERs were most sensitive to the cost of pembrolizumab and the ICERs exceeded $150,000/QALYs in all subgroups.ConclusionsEvidence suggests that first-line pembrolizumab in combination with chemotherapy is not a cost-effective option for advanced esophageal cancer in the US, regardless of PD-L1 expression status.
| S-EPMC10028044 | biostudies-literature
Project description:BackgroundRecent phase III randomized controlled trials have demonstrated that first-line immune checkpoint inhibitors (ICIs) improve prognosis in advanced HER-2-negative gastric cancer patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) higher than 5. However, these findings are not confirmed in real-world settings, and the benefits in PD-L1 CPS < 5 patients remain controversial.MethodsIn this multicenter, retrospective cohort study, data from across thirteen medical centers were analyzed by inverse probability of treatment weighting for matching, alongside univariate and multivariate COX proportional hazard regression models. Genomic and transcriptomic analyses were conducted to identify efficacy prognostic models and resistance mechanisms.ResultsThis study included 573 patients with advanced gastric cancer, 265 treated with chemotherapy and 308 with ICIs plus chemotherapy. In the overall cohort and HER-2-negative patients, the combination therapy significantly improved progression-free survival and overall survival, without marked increases in severe adverse events. Notably, patients with PD-L1 CPS 1-4 showed significant overall survival prolongation and a trend towards improved progression-free survival with combination therapy. Patients with unknown PD-L1 status also benefitted from ICIs. SMARCA4 and BRCA2 mutations were more frequent in patients with responses, while CCNE1 and ZFHX3 alternation, alongside high "ABC transporters" signatures, were more common in non-responsive patients. A novel risk model, PGFIC, outperformed traditional biomarkers in predicting treatment outcomes.ConclusionsAdding ICIs to first-line treatment significantly prolongs survival in overall patients and in those with PD-L1 CPS 1-4 or unknown. This study also provides valuable insights into prognostic markers and resistance mechanisms, potentially guiding immunotherapy strategies.
| S-EPMC11657984 | biostudies-literature
Project description:BackgroundThis study evaluated the cost-effectiveness of nivolumab plus chemotherapy (NC) or ipilimumab versus chemotherapy as a first-line treatment for advanced esophageal squamous cell carcinoma (ESCC) in the United States and China.MethodsA partitioned survival model was constructed from the perspective of the US third-party payers and Chinese healthcare system. Health states and transition probabilities were modeled based on the survival data from the CheckMate-648 clinical trial (NCT03143153). The time horizon for the model was 10 years. Only direct medical costs were considered. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of the results.ResultsIn the United States, nivolumab plus ipilimumab (NI) led to an incremental cost-effectiveness ratio (ICER) of $155,159.82/quality-adjusted life year (QALY) and $104,297.07/QALY gained in the overall population and in patients with tumor cell programmed death-ligand 1 (PD-L1) expression of ⩾1% (subgroup), respectively. The ICER for the subgroup was between the willingness-to-pay (WTP) threshold values of $100,000/QALY and $150,000/QALY, and the other case was higher than $150,000/QALY. NC led to an ICER of $518,062.85/QALY and $193,169.49/QALY gained in the overall population and the subgroup, respectively. Both ICERs were significantly higher than the WTP threshold of $150,000/QALY. In China, the ICERs for patients treated with the addition of nivolumab were >$90,000/QALY in all cases, significantly exceeding the WTP threshold of $37,654/QALY.ConclusionsNI is more cost-effective than NC or chemotherapy alone for treating advanced ESCC with PD-L1 expression ⩾1% in the United States. Chemotherapy alone is the only cost-effective option in China.
| S-EPMC9486256 | biostudies-literature
Project description:AimsTo investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC).Materials and methodsIn this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups.ResultsOf the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12-2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13-4.44; p = 0.033).ConclusionIn patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.
| S-EPMC10725584 | biostudies-literature
Project description:Chemotherapy in combination with immune checkpoint inhibitor (ICI) or bevacizumab has demonstrated a superior effect for non-squamous non-small cell lung cancer (NS-NSCLC). There are still few randomized controlled trials (RCTs) investigating the differences between ICI plus chemotherapy (ICI-chemotherapy) and bevacizumab plus chemotherapy (Bev-chemotherapy) in first-line treatment of NS-NSCLC. We identified RCTs in databases and conference abstracts presented at international conferences by Sep 1, 2021. Bayesian network meta-analysis was performed using randomized effect consistency model to estimate hazard ratio (HR) and odds ratio (OR). The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥ 3 treatment-related adverse events (TRAEs). Fifteen RCTs (17 articles) of 6561 advanced NS-NSCLC patients receiving ICI-chemotherapy, Bev-chemotherapy, or chemotherapy at first-line were eligible for analysis. NMA results showed that first-line ICI-chemotherapy prolonged OS (HR 0.79, 0.66-0.94) in patients with advanced NS-NSCLC compared with Bev-chemotherapy, while no differences were in PFS, ORR, and grade ≥ 3 TRAEs (p > 0.05). Ranking plots suggested that ICI-chemotherapy had the most probability to offer the best OS (probability 0.993), PFS (probability 0.658), and ORR (probability 0.565), and Bev-chemotherapy had the most risks of grade ≥ 3 TRAEs (probability 0.833). Therefore, our findings showed that first-line ICI-chemotherapy was associated with better OS than Bev-chemotherapy in patients with advanced NS-NSCLC, and more clinical trials are warranted to confirm these results.
| S-EPMC9119358 | biostudies-literature
Project description:IntroductionPlatin-based chemotherapy (CT) has long been the first-line standard-of-care for patients with extensive-stage small-cell lung cancer (ES-SCLC). Adding immune-checkpoint inhibitor(s) to CT (ICI+CT) in this setting is an option of interest, although its benefit is apparently modest.MethodsThis meta-analysis was conducted on randomized trials comparing first-line ICI+CT versus CT alone for ES-SCLC. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), response at 12 months and adverse events (AEs). Subgroup analyses were computed according to the immunotherapy used, performance status (PS), age, platinum salt, liver metastases and brain metastases at diagnosis.ResultsThe literature search identified one randomized phase II (ECOG-ACRIN-5161) and four phase III trials (CASPIAN, IMPOWER-133, KEYNOTE-604 and Reck et al. 2016) that included 2775 patients (66% males, 95% smokers, median age: 64 years, PS = 0 or 1). ICI+CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS [0.82 (0.75-0.89); p < 0.00001] and PFS [0.81 (0.75-0.87); p < 0.00001], with OS benefits for anti-PD-L1 [0.73 (0.63-0.85); p < 0.0001] or anti-PD-1 [0.76 (0.63-0.93); p < 0.006] but not for anti-CTLA-4 [0.90 (0.80-1.01), p = 0.07]. ORRs for ICI+CT or CT alone were comparable [odds ratio 1.12 (0.97-1.00); p = 0.12], but responses at 12 months favored ICI+CT [4.16 (2.81-6.17), p < 0.00001]. Serious grade-3/4 AEs were more frequent with ICI+CT [odds ratio 1.18 (1.02-1.37); p = 0.03]. Compared with CT, no ICI+CT benefit was found for ES-SCLC with brain metastases at diagnosis [HR 1.14 (0.87-1.50); p = 0.34].ConclusionsFirst-line ICI+CT appears to be superior to CT alone for ES-SCLC except for patients with brain metastases at diagnosis.
| S-EPMC7731693 | biostudies-literature
Project description:Rare cancers present significant challenges in diagnosis, treatment, and research, accounting for up to 25% of global cancer cases. Due to their rarity and atypical presentations, they are often misdiagnosed, resulting in late-stage detection and poor outcomes. Here, we describe a patient case with advanced metastatic nasopharynx NUT carcinoma, one of the rarest and most aggressive cancers. We conducted a comprehensive analysis of this patient's tumor, including Tumor Mutation Burden, Microsatellite Instability, and genetic profiling to explore further putative druggable targets. The tumor exhibited high PD-L1 expression and showed a notable response to immune checkpoint inhibitors when combined with platinum-based radio-chemotherapy. Our findings indicate that checkpoint inhibitors could play a critical role in treating NUT carcinoma, offering new therapeutic avenues and hope for patients with this challenging diagnosis. Whether PD-L1 expression may be a useful predictor of immune checkpoint inhibitor efficacy warrants further research.
| S-EPMC11762287 | biostudies-literature
Project description:In BRAF wild type advanced melanoma, immune checkpoint blockers such as anti-PD1 (anti-programmed cell death 1) are usually continued beyond progression for a hypothetical rare further response. Chemotherapy as a second-line option is considered ineffective by many practitioners based on historical data. Continuing anti-PD1 beyond progression has a high health-economic impact and is not recommended by the FDA. This study aimed to describe the efficacy and survival of advanced melanoma patients who received second-line (or more) chemotherapy after immunotherapy failure.This was a retrospective single center study conducted in a French University Hospital during an 11-month period. All advanced melanoma patients treated with chemotherapy after immunotherapy failure were included.Eighteen patients were analyzed. Therapeutic response to chemotherapy was evaluable in 16 patients: partial response was achieved in 3/16 (19%), stable disease in 1/16 (6%) and progressive disease in 12/16 (75%). Median overall survival from chemotherapy start was 12 months. Median progression-free survival was 5.4 months. The 6-month overall survival rate was 81% and the 6-month progression-free survival rate was 40%.Although the disease control rate with chemotherapy was low (25%), survival data in our study are far superior to those previously published. This could be linked to a high proportion of patients treated with anti-PD1 just prior to chemotherapy, which may suggest a potential synergy between immunotherapy and chemotherapy.
| S-EPMC7373626 | biostudies-literature