Outstanding clinical efficacy of PD-1/PD-L1 inhibitors for pulmonary pleomorphic carcinoma.

We evaluated programmed death ligand 1 (PD-L1) expression and efficacy of PD-1/PD-L1 inhibitors in patients with pulmonary pleomorphic carcinoma (PC). We created two cohorts of patients diagnosed with pulmonary PC from 2016 to 2019, PD-L1 expression and programmed death 1 (PD-1)/PD-L1 inhibitor efficacy cohorts. The PD-L1 expression cohort included all patients evaluated for PD-L1 expression, irrespective of PD-1/PD-L1 inhibitor therapy. High PD-L1 expression was defined as ≥50% positive tumour cells (TC) for 22C3, ≥25% for SP263 or ≥10%/5% TC/immune cell (IC) for SP142. The PD-1/PD-L1 efficacy cohort included patients treated with PD-1/PD-L1 inhibitors, irrespective of PD-L1 tests. One hundred twenty-five of 175 patients diagnosed with pulmonary PCs were included in the PD-L1 expression cohort. Among them, 112 patients (89.6%) had PD-L1-positive (≥1%) tumours and 100 (80.0%) had tumours with high PD-L1 expression. A total of 49 patients were included in the efficacy cohort: 40 received pembrolizumab, 7 nivolumab and 2 atezolizumab. The objective response rate was 49.0%, with a median progression-free survival (PFS) of 7.2 months and a median overall survival of 22.2 months. In the efficacy cohort, high PD-L1 expression (n = 41) was associated with longer PFS (median: 7.2 versus 1.5 months, hazard ratio [HR]: 0.53 [0.22-1.29], p = 0.16) and overall survival (median: 22.2 versus 3.5, HR: 0.21 [0.08-0.57], p = 0.001) than low/negative/unknown PD-L1 expression (n = 8). PD-1/PD-L1 inhibitors show outstanding efficacy for pulmonary PCs, and this is possibly attributable to high PD-L1 expression in these tumours.

Lee J ，Choi Y ，Jung HA ，Lee SH ，Ahn JS ，Ahn MJ ，Park K ，Sun JM ... -  《-》

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression.

In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes . Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.

Aguilar EJ ，Ricciuti B ，Gainor JF ，Kehl KL ，Kravets S ，Dahlberg S ，Nishino M ，Sholl LM ，Adeni A ，Subegdjo S ，Khosrowjerdi S ，Peterson RM ，Digumarthy S ，Liu C ，Sauter J ，Rizvi H ，Arbour KC ，Carter BW ，Heymach JV ，Altan M ，Hellmann MD ，Awad MM ... -  《-》

Efficacy of anti-PD-1 antibodies in NSCLC patients with an EGFR mutation and high PD-L1 expression.

Masuda K ，Horinouchi H ，Tanaka M ，Higashiyama R ，Shinno Y ，Sato J ，Matsumoto Y ，Okuma Y ，Yoshida T ，Goto Y ，Yamamoto N ，Ohe Y ... -  《-》

Efficacy of immune checkpoint inhibitors according to PD-L1 tumor proportion scores in non-small cell lung cancer.

We correlated the tumor proportion score (TPS) of programmed cell death ligand 1 (PD-L1, SP263 or 22C3) expression with the disease control rate (DCR, partial remission and stable disease), and progression free survival (PFS) after nivolumab or pembrolizumab treatment. A total of 70 case records (55 males, 15 females) of patients with non-small cell lung cancer (NSCLC, 46 adenocarcinoma, 22 squamous cell carcinoma, and two others) were reviewed. The PD-L1 expressions were divided into High (SP263 ≥ 30%, 22C3 ≥ 80%) and Low groups (SP263 < 30%, 22C3 < 80%). In the combined analysis, the PD-L1 group was defined as High if either of the two stains was classified as High and defined as Low if both stains were classified as Low. Among the patients treated with nivolumab (n = 37), the SP263 High group showed higher DCR compared to the SP263 Low group (52.6% vs. 11.1%, P = 0.024). In patients treated with pembrolizumab (n = 33), no significant difference in DCR and PFS according to PD-L1 expression was observed. In the combined analysis (n = 36), patients in the PD-L1 High group showed significantly higher DCRs than those in the PD-L1 Low group (56.1% vs. 24.1%, P = 0.028). PFS was significantly longer in the PD-L1 High group than in the Low group (medians 4.1 vs. 1.6 months, respectively, P = 0.04). A high expression level of PD-L1 was correlated with a significantly higher DCR and longer PFS in NSCLC patients treated with nivolumab or pembrolizumab.

Park S ，Choi YD ，Kim J ，Kho BG ，Park CK ，Oh IJ ，Kim YC ... -  《-》

Outcome of Patients with Non-Small Cell Lung Cancer and Brain Metastases Treated with Checkpoint Inhibitors.

Although frequent in NSCLC, patients with brain metastases (BMs) are often excluded from immune checkpoint inhibitor (ICI) trials. We evaluated BM outcome in a less-selected NSCLC cohort. Data from consecutive patients with advanced ICI-treated NSCLC were collected. Active BMs were defined as new and/or growing lesions without any subsequent local treatment before the start of ICI treatment. Objective response rate (ORR), progression-free survival, and overall survival (OS) were evaluated. Multivariate analyses were performed by using a Cox proportional hazards model and logistic regression. A total of 1025 patients were included; the median follow-up time from start of ICI treatment was 15.8 months. Of these patients, 255 (24.9%) had BMs (39.2% active, 14.3% symptomatic, and 27.4% being treated with steroids). Disease-specific Graded Prognostic Assessment (ds-GPA) score was known for 94.5% of patients (35.7% with a score of 0-1, 58.5% with a score of 1.5-2.5, and 5.8% with a score of 3). The ORRs with BM versus without BM were similar: 20.6% (with BM) versus 22.7% (without BM) (p = 0.484). The intracranial ORR (active BM with follow-up brain imaging [n = 73]) was 27.3%. The median progression-free survival times were 1.7 (95% confidence interval [CI]: 1.5-2.1) and 2.1 (95% CI: 1.9-2.5) months, respectively (p = 0.009). Of the patients with BMs, 12.7% had a dissociated cranial-extracranial response and two (0.8%) had brain pseudoprogression. Brain progression occurred more in active BM than in stable BM (54.2% versus 30% [p < 0.001]). The median OS times were 8.6 months (95% CI: 6.8-12.0) with BM and 11.4 months (95% CI: 8.6-13.8) months with no BM (p = 0.035). In the BM subgroup multivariate analysis, corticosteroid use (hazard ratio [HR] = 2.37) was associated with poorer OS, whereas stable BMs (HR = 0.62) and higher ds-GPA classification (HR = 0.48-0.52) were associated with improved OS. In multivariate analysis BMs are not associated with a poorer survival in patients with ICI-treated NSCLC. Stable patients with BM without baseline corticosteroids and a good ds-GPA classification have the best prognosis.

Hendriks LEL ，Henon C ，Auclin E ，Mezquita L ，Ferrara R ，Audigier-Valette C ，Mazieres J ，Lefebvre C ，Rabeau A ，Le Moulec S ，Cousin S ，Duchemann B ，le Pechoux C ，Botticella A ，Ammari S ，Gazzah A ，Caramella C ，Adam J ，Lechapt E ，Planchard D ，De Ruysscher D ，Dingemans AM ，Besse B ... -  《-》