Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC.

CD73 induces the dephosphorylation of adenosine monophosphate converting it to adenosine, enabling malignancies to escape from immune surveillance. Although CD73 overexpression has been reported to be a poor prognostic factor in several malignancies including non-small cell lung cancer (NSCLC), its predictive relevance in NSCLC patients receiving immune checkpoint inhibitors is unknown. The present research was conducted to investigate the prognostic significance of CD73 expression in NSCLC patients receiving immune checkpoint inhibitors (ICIs). We screened 91 patients with advanced or recurrent NSCLC who received immune checkpoint inhibitors. CD73 expression was evaluated immunohistochemically using tissue specimens obtained just before treatment with ICIs. Analysis of progression-free survival (PFS) and overall survival (OS) in relation to several levels of CD73 expression (1%, 10%, 30%, and 50%) showed that both tended to be more favorable as expression of CD73 increased. PFS and OS were longer for patients in whom at least 50% of the tumor cells expressed CD73 than for those in whom <50% of the tumor cells did so. In patients who were positive for EGFR mutation, immune checkpoint inhibitors were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation-negative NSCLC. Furthermore, CD73 expression was predictive factor for the PFS independent of PD-L1 expression in patients with EGFR mutation. High CD73 expression may predict a favorable response to ICIs in NSCLC patients, especially those harboring EGFR mutations. Significant findings of the study: In patients who were positive for EGFR mutation, immune checkpoint inhibitors (ICIs) were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation-negative NSCLC. High CD73 expression may predict a favorable response to immune checkpoint inhibitors in NSCLC patients, especially those harboring EGFR mutations.

Ishii H ，Azuma K ，Kawahara A ，Kinoshita T ，Matsuo N ，Naito Y ，Tokito T ，Yamada K ，Akiba J ，Hoshino T ... -  《-》

Association Between Clinical Tumor Burden and Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non-Small-Cell Lung Cancer.

Programmed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non-small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relationship has remained unclear for NSCLC. The present single-center retrospective study evaluated 163 patients with advanced NSCLC who had received PD-1/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy from December 2015 to December 2018. The clinical tumor burden was estimated using the baseline sum of the target lesions' longest diameters (BSLDs), measured according to the Response Evaluation Criteria for Solid Tumors, and the baseline number of metastatic lesions (BNMLs). The optimal cutoff values for predicting progression-free survival (PFS) were 5 for the BNMLs and 76 mm for the BSLDs, using the minimum P value method. The low-BNML group included 73 patients (44.8%). The median PFS was 12.2 months in the low-BNML group and 2.8 months in the high-BNML group (hazard ratio, 0.51; P = .0005). The low-BSLD group included 92 patients (56.4%). The median PFS was 9.6 months in the low-BSLD group and 3.4 months in the high-BSLD group (hazard ratio, 0.52; P = .0006). Multivariable analysis revealed that low-BSLD, low-BNML, nonsquamous histologic type and a PD-L1 tumor proportion score of ≥ 50% were independently associated with prolonged PFS. PD-L1 expression and the clinical tumor burden can predict the efficacy of PD-1/PD-L1 inhibitor monotherapy for NSCLC.

Miyawaki T ，Kenmotsu H ，Mori K ，Miyawaki E ，Mamesaya N ，Kawamura T ，Kobayashi H ，Omori S ，Wakuda K ，Ono A ，Naito T ，Murakami H ，Harada H ，Endo M ，Ohde Y ，Takahashi K ，Takahashi T ... -  《-》

Immunotherapy as second-line treatment and beyond for non-small cell lung cancer in a single center of China: Outcomes, toxicities, and clinical predictive factors from a real-world retrospective analysis.

Real-world evidence of second-line treatment and beyond with immune checkpoint inhibitors (ICIs) in Chinese patients is lacking. Here, we aimed to assess the efficacy, responses, and immune-related side effects of anti-PD-1 agents in real-life practice. We retrospectively analyzed consecutive patients who received nivolumab or pembrolizumab monotherapy at Peking Medical College Hospital. We collected baseline characteristics, evaluated treatment efficacy, and categorized immune-related adverse effects (irAEs). Predictive factors of treatment response were also determined. The study included 97 patients with a median age of 64 years. The majority of patients were male, with nonsquamous histological type and advanced stage tumor, and had a history of smoking. Most patients received ICIs as second-line therapy. Expression of PD-L1 was detected in 34.11% patients. Overall response rate (ORR) and disease control rate (DCR) were 16.49% and 60.82%, respectively. None of the patients achieved complete response (CR). The median PFS and OS were150 days and 537 days, respectively. The incidence of immune-related toxicities was similar to the one previously reported. Patients with driver gene mutations had shorter PFS than patients without, while patients who encountered irAE had relatively longer PFS. The real-world clinical outcome of ICIs in second- and further-line NSCLC therapy is promising. Several characteristics may have predictive value for efficacy. Occurrence of irAEs during treatment was acceptable and could be an independent positive predictive for PFS. SIGNIFICANT FINDINGS OF THE STUDY: Efficacy and safety profile of ICIs as second-line treatment or above for patients with NSCLC are promising in real world circumstances Incidence and median time to the occurrence of irAEs vary between organs WHAT THIS STUDY ADDS: Driver gene mutations are associated with lower progression-free survival Occurrence of irAEs is associated with higher progression-free survival.

Chen M ，Li Q ，Xu Y ，Zhao J ，Zhang L ，Wei L ，Zhong W ，Wang M ... -  《-》

Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non-small cell lung cancer.

CD47 is an antiphagocytic molecule that contributes to tumor cell resistance in host immune surveillance. CD47 overexpression correlated with tumor progression and shorter survival in lung cancer. However, the expression and functional significance of CD47 in Non-Small Cell Lung Cancer (NSCLC) has not been completely understood. In this retrospective study, CD47 expression was immunohistochemically examined in tumor biopsies from 169 NSCLC patients. The association of CD47 levels (H-score) with clinicopathological characteristics and survival outcomes was evaluated. CD47 protein was detected in 84% of patients with a median expression of 80% (0-100). Tumor CD47 levels above 1% and 50% were found in 84% and 65.7% of patients, respectively. While, median CD47 staining index was 160 (0-300). Patients were divided into two groups according to CD47 expression (high or low), using a cutoff value of 150. High CD47 expression was associated with wood smoke exposure (71.1% vs 28.9%, P = .013) and presence of EGFR (+) mutations (66.7% vs 33.3%, P = .04). Survival analysis carried out in the whole population did not show any association of CD47 expression and survival outcome. However, in patients with EGFR (+) mutations, CD47 expression was associated with higher progression-free survival (PFS) (12.2 vs. 4.4 months, P = .032). When the survival analysis was performed according to CD47 levels (cut off value: 150), both, PFS and overall survival (OS) were shortened in patients with a high expression of CD47 (10.7 vs. NR, P = .156) and (29.2 vs. NR months P = .023), respectively. CD47 overexpression is not a prognostic factor for PFS and OS in NSCLC patients. However, the presence of EGFR mutations and high expression of CD47 were associated with shortened PFS and OS. Coexpression of these markers represents a potential biomarker and characterizes a therapeutic niche for lung cancer.

Arrieta O ，Aviles-Salas A ，Orozco-Morales M ，Hernández-Pedro N ，Cardona AF ，Cabrera-Miranda L ，Barrios-Bernal P ，Soca-Chafre G ，Cruz-Rico G ，Peña-Torres ML ，Moncada-Claudio G ，Ramirez-Tirado LA ... -  《Cancer Medicine》

Switching administration of anti-PD-1 and anti-PD-L1 antibodies as immune checkpoint inhibitor rechallenge in individuals with advanced non-small cell lung cancer: Case series and literature review.

Based on several phase III studies, immune checkpoint inhibitors (ICIs) are essential and promising drugs for the treatment of non-small cell lung cancer (NSCLC). However, in patients previously treated with ICI, the efficacy and safety of rechallenging the same or another type of ICI inhibitor remain unclear. Moreover, clinical data about the efficacy of switching the administration of anti-programmed death-1 (PD-1) antibodies (e.g. nivolumab, pembrolizumab) and anti-programmed death-ligand 1 (PD-L1) antibodies (e.g. atezolizumab) as ICI rechallenge are limited. Thus, the current study aimed to evaluate the efficacy and safety of such treatment strategy in NSCLC patients. We retrospectively reviewed the medical records of 17 patients with advanced or recurrent NSCLC who received both anti-PD-1 and anti-PD-L1 antibodies during their clinical courses. Among the 17 patients, one (5.9%) and nine (52.9%) achieved partial response and stable disease, respectively, after ICI rechallenge. The median progression-free survival of ICI rechallenge in these patients was 4.0 (range: 0.4-8.0) months, and the median overall survival from the start of the initial ICI was 31.0 (range: 7.6-46.8) months. Of the 10 patients who developed immune-related adverse events (irAEs) during the first ICI treatment, five presented with these events after the readministration of ICI. Among them, four experienced relapsed irAEs and two patients had pneumonitis, which is a grade 3 or higher irAE. Almost all irAEs during the rechallenge treatment were manageable. Switching the administration of anti-PD-1 and anti-PD-L1 antibodies as ICI rechallenge could be a treatment option for some NSCLC patients. • Significant findings of the study In this study, switching the administration of anti-PD-1 and anti-PD-L1 antibodies as ICI rechallenge could be an effective and safe treatment option for some patients with advanced or recurrent NSCLC. • What this study adds Switching the administration of ICI may increase the efficacy of readministration. However, the mechanism is unknown. Thus, further accumulation of cases is required, and extensive investigations must be conducted to elucidate the mechanism and benefits of such treatment.

Kitagawa S ，Hakozaki T ，Kitadai R ，Hosomi Y ... -  《-》