Comparison of a combination of chemotherapy and immune checkpoint inhibitors and immune checkpoint inhibitors alone for the treatment of advanced and metastatic non-small cell lung cancer.

Single agent immune checkpoint inhibitors (ICIs) improve survival outcomes compared to chemotherapy for advanced non-small cell lung cancer (NSCLC), but treatment efficacy widely varies. The combination of ICIs with chemotherapy has shown promising efficacy over chemotherapy alone; however, whether this strategy is superior to single agent ICIs for the treatment of advanced NSCLC remains unknown. The records of 109 patients with advanced NSCLC who were administered at least one cycle of ICIs were retrospectively reviewed. Patients were grouped based on the presence or absence of a chemotherapy treatment combination. Efficacy and survival outcomes were analyzed. Sixty-nine (58.0%) patients received single agent ICIs (ICI group) and 50 (42.0%) received ICIs and chemotherapy (ICC group). The median (3.2 vs. 3.0 months; P = 0.025) and one-year (34.5 vs. 9.6%; P = 0.026) progression-free survival (PFS) rates were significantly better in the ICC than in the ICI group. The superior efficacy of ICC remained in the propensity score matched pairs (median PFS 3.2 vs. 2.6 months, P = 0.032; 1-year PFS 35.2 vs. 7.6%; P = 0.035). Eastern Cooperative Oncology Group performance status 0-1 (HR 0.37, 95% CI 0.22-0.62; P < 0.001) and the ICC group (HR 0.56, 95% CI 0.34-0.94; P = 0.028) were predictive of PFS. Subgroup-to-chemotherapy interaction revealed improved risk reduction for adenocarcinoma and EGFR mutation. Combing chemotherapy with ICIs improved treatment efficacy over ICIs alone. The additional efficacy of chemotherapy may differ between histological subtypes and EGFR mutation status.

Kuo CS ，Wang CC ，Huang YC ，Pavlidis S ，Liu CY ，Ko HW ，Chung FT ，Lin TY ，Wang CL ，Guo YK ，Yang CT ... -  《-》

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 ... -  《-》

High mortality and poor treatment efficacy of immune checkpoint inhibitors in patients with severe grade checkpoint inhibitor pneumonitis in non-small cell lung cancer.

The treatment efficacy of immune checkpoint inhibitor (ICI) and clinical outcomes in patients with non-small cell lung cancer (NSCLC) who develop severe grade checkpoint inhibitor pneumonitis (CIP) are unclear. Here, we report on the treatment efficacy of ICI and prognosis in NSCLC patients with severe grade CIP. In this retrospective cohort study, CIP severity, CIP-related mortality, and ICI efficacy in 71 patients with advanced NSCLC treated with ICIs were evaluated. Data was obtained from the patients' medical charts. All grade and severe grade CIP were observed in 22 and 11 patients, respectively. The CIP-related mortality rate was 22.7% (N = 5). An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of ≥2 and pre-existing interstitial lung disease (ILD) were significantly associated with the development of severe grade CIP (P = 0.001 and P = 0.035, respectively). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with severe grade CIP than in those without severe grade CIP (PFS 1.0 month, 95% confidence interval [CI] 0.5-2.0 vs. 3.5 months, 95% CI 2.0-5.0 months, P = 0.003; OS 3.0 months, 95% CI 0.5-13 vs. 12.7 months, 95% CI 8.0-21.0 months, P = 0.011). CIP is a serious complication with a poor prognosis associated with high mortality. The efficacy of ICI is significantly worse in patients with severe grade CIP than in those without severe grade CIP. Whether ICIs should be administered to patients with CIP risk factors, such as an ECOG PS score of ≥2 or pre-existing ILD, should be carefully assessed.

Tone M ，Izumo T ，Awano N ，Kuse N ，Inomata M ，Jo T ，Yoshimura H ，Minami J ，Takada K ，Miyamoto S ，Kunitoh H ... -  《-》

Rational application of the first-line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta-analysis.

To compare the relative efficacy of immune checkpoint inhibitors (ICIs) or chemotherapy (CT) alone, or their combination modality in the first-line treatment of advanced nonsmall cell lung cancer (NSCLC). This meta-analysis was performed on the eligible randomized controlled trials (RCTs) after searching web databases and meeting abstracts. The main research endpoints were the comparisons of median overall survival (mOS), the OS rate of 6 months (OSR6m), 1 year (OSR1y) and 2 years (OSR2y), median progression-free survival (mPFS), the PFS rate of 6 months (PFSR6m) and 1-year (PFSR1y), objective response rates (ORR), and treatment-related adverse events (TRAEs). Eleven RCTs comprising 6278 cases were included. In the subgroup of programmed death-ligand 1 (PD-L1) ≥50%, compared with chemotherapy, the ICIs showed similar OSR6m (P > 0.05), but significantly improved efficacy in mOS, OSR1y, OSR2y, and ORR (all P < 0.05), also had less grade ≥ 3 TRAEs. Compared with pembrolizumab alone, pembrolizumab plus CT in the subgroup of PD-L1 ≥ 50% had similar mOS, OSR6m, OSR1y, and PFSR1y (all P > 0.05), but significantly improved mPFS, PFSR6m, and ORR (all P < 0.05 for interaction). Compared with the CT group, ICIs plus CT group with PD-L1 ≥ 50% or <1% showed significant benefit in OS, PFS, and ORR (all P < 0.05). However, in the ICIs plus CT group with 1% ≤ PD-L1 ≤ 49%, only PFS and ORR showed significant benefit compared with CT group (all P < 0.05), but not for results of OS. The findings support the rationale for using pembrolizumab alone in the first-line treatment of PD-L1 ≥ 50% advanced NSCLC due to the similar OS and lower grade ≥ 3 TRAEs. However, the combination of ICIs and chemotherapy is strongly recommended in patients with PD-L1 ≤ 49% for significant survival benefit.

Cao R ，Ma JT ，Zhang SL ，Sun L ，Liu Y ，Zhang XY ，Jing W ，Huang LT ，Han CB ... -  《Cancer Medicine》

Immunotherapy Alone or in Combination with Chemotherapy as First-Line Treatment of Non-Small Cell Lung Cancer.

Saxena P ，Singh PK ，Malik PS ，Singh N ... -  《-》