Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis.
This network meta-analysis (NMA), based on 12 phase-III studies with 9,236 metastatic NSCLC patients, aims to compare the efficacy of treatments including at least one immune-checkpoint inhibitor (ICI) with or without chemotherapy, as frontline therapy for advanced NSCLC patients. The NMA includes direct randomized evidence on treatments of interest along with indirect evidence from randomized studies with chemotherapy as the common comparator. Studies were identified by searching PubMed, and the abstracts of most recent main oncology congresses. The primary endpoint, Hazard-Ratio (HR) of Progression-free Survival (PFS), was estimated by a frequentist-approach NMA. Results are presented in the overall cohort (all-comers or PD-L1-positive) irrespective of histology, and by histology, PD-L1 expression level and sex. According to the primary PFS-NMA in the overall cohort, the combination of chemotherapy, first with pembrolizumab, second with atezolizumab exhibit significantly higher benefit than any other treatment examined. This superior PFS benefit is found for both squamous and non-squamous patients. Similarly for OS, the combination of pembrolizumab/chemotherapy, and atezolizumab/bevacizumab/chemotherapy-(ABC), followed by pembrolizumab-monotherapy and atezolizumab/chemotherapy, are the best treatments in the overall cohort, driven by the non-squamous histology. In the PD-L1-high patients again the combination of chemotherapy with atezolizumab or pembrolizumab, exhibit significant PFS benefit, followed by pembrolizumab-monotherapy. PFS benefit of these ICI/chemotherapy combinations are also found in PD-L1-negative and PD-L1-intermediate patients(1%≤PD-L1 < 50%). Of note, ABC is evaluated only for OS in non-squamous patients while the pembrolizumab-monotherapy PFS benefit and the atezolizumab/chemotherapy OS benefit are probably under-estimated since most of the data stems from non-significant interim analyses of ongoing studies [KN042;IM131/132/150]. In conclusion, the addition of chemotherapy to ICIs enhanced their treatment efficacy as first-line treatment for advanced NSCLC patients. The combination of chemotherapy with either pembrolizumab or atezolizumab show consistently higher efficacy than chemotherapy-alone or any other ICI-combination or monotherapy, particularly in non-squamous patients.
Dafni U
，Tsourti Z
，Vervita K
，Peters S
... -
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Serum Tumor Marker Dynamics as Predictive Biomarkers in NSCLC Chemo-Immunotherapy and Mono-Immunotherapy Maintenance: A Registry-Based Descriptive Study.
To evaluate serum tumor markers (STM) as predictive biomarkers in advanced non-small cell lung cancer (NSCLC) treated with chemo-immunotherapy.
Patients having received platinum-based chemo-(CHT) and PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) combination therapy were retrospectively followed. Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cytokeratin-19 fragments (CYFRA 21-1) and neuron specific enolase (NSE) were routinely measured at NSCLC diagnosis. The marker with the highest relative elevation was defined "leading STM", its change was assessed between CHT-ICI as well as mono-ICI maintenance initiation and the respective subsequent restaging. Corresponding computed tomography evaluations were analyzed using response evaluation criteria in solid tumors (RECIST). For CHT-ICI combination and subsequent mono-ICI-maintenance therapy, leading STM and RECIST response were evaluated regarding progression-free (PFS) and overall survival (OS) in Kaplan-Meier analyses.
Among 80 CHT-ICI patients (41% women, mean age 63 years), median PFS was 5 months (M;4,9), median OS was 15M (10,/). PFS was significantly (p=0.042) longer, when the leading STM had decreased at first restaging under CHT-ICI combination therapy (9M (5,12; n=41) vs 5M (3,6; n=16)). In the 54 (67.5%) patients who received subsequent mono-ICI maintenance therapy, STM decrease was similarly associated with significantly (p<0.001) longer PFS (16M (7,/; n=16) vs 3.5M (2,6; n=22)). Patients with radiologically stable or progressive disease and concomitant leading STM decrease had similar PFS in the CHT-ICI combination phase (4M (3,7; n=16) vs 4.5M (2,6; n=14)), but longer PFS in the mono-ICI maintenance setting (13M (7,16; n=10) vs 3M (2,4; n=17)). Median OS was not reached in most subgroups.
Leading STM dynamics provide predictive biomarker information additional to radiological response evaluation patients receiving CHT-ICI combination therapy, especially in the mono-ICI maintenance setting.
Lang D
，Haslinger W
，Akbari K
，Scala M
，Hergan B
，Asel C
，Horner A
，Wass R
，Brehm E
，Kaiser B
，Lamprecht B
... -
《Lung Cancer-Targets and Therapy》
Immune checkpoint inhibitor (ICI)-based treatment beyond progression with prior immunotherapy in patients with stage IV non-small cell lung cancer: a retrospective study.
Although immune checkpoint inhibitors (ICIs) provide unprecedented survival improvement for patients with advanced non-small cell lung cancer (NSCLC), disease progression inevitably occurs. After ICIs failure, limited data exist on whether ICI-based treatment beyond progression (TBP) may be beneficial to advanced NSCLC. This retrospective study aimed to evaluate the efficacy of this treatment approach in advanced NSCLC and identify potential beneficial factors.
Patients with stage IV NSCLC who received ICI-based treatment after the failure of prior PD-1/PD-L1 inhibitor treatments (monotherapy or combination therapy) between January 2016 and July 2020 were enrolled. Their clinical characteristics and treatment procedures were collected, and the follow-up would be performed.
A total of 204 patients were included. All patients had disease progression after prior immunotherapy, with 49.5% (101/204) of patients presenting with new metastasis lesions and the rest 50.5% (103/204) of patients' progression on originate lesions. Within the entire cohort, the median progression-free survival (PFS) and median overall survival (OS) of ICI-based TBP with prior immunotherapy were 5.0 months (95% CI: 4.5-5.5 months) and 15.7 months (95% CI: 14.7-16.8 months), respectively. The objective response rate (ORR) and disease control rate (DCR) were 9.3% and 74.0%, respectively. According to the multivariate analysis, ICI-based combination therapy [PFS: hazard ratio (HR), 0.48, 95% confidence interval (CI): 0.28-0.84, P=0.011] (OS: HR, 0.44, 95% CI: 0.23-0.85, P=0.014), not having targetable gene alterations (PFS: HR, 0.56, 95% CI: 0.40-0.79, P=0.001) (OS: HR, 0.57, 95% CI: 0.37-0.87, P=0.009), and good response to prior immunotherapy (PFS: HR, 0.36, 95% CI: 0.24-0.53, P<0.0001) (OS: HR, 0.31, 95% CI: 0.19-0.52, P<0.0001) were independently associated with improved PFS and OS. Moreover, disease progression due to appearances of new metastasis (OS: HR, 0.56, 95% CI: 0.37-0.84, P=0.005) was only associated with better OS.
While the ORR in patients with advanced NSCLC receiving ICI-based TBP with prior immunotherapy was limited, the DCR was relatively high in our study which is encouraging. ICI-based treatment strategy may be a reasonable option for patients who progressed from prior immunotherapy. Further prospective studies on larger sample size are warranted.
Tian T
，Yu M
，Yu Y
，Wang K
，Tian P
，Luo Z
，Ding Z
，Wang Y
，Gong Y
，Zhu J
，Zou B
，Sio TT
，Alves A
，Liu Y
，Huang M
，Lu Y
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ResearchGate
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钛学术
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