Comparing three different anti-PD-L1 antibodies for immunohistochemical evaluation of small cell lung cancer

Yoshimura, Akihiro; Yamada, Tadaaki; Miyagawa‐Hayashino, Aya; Sonobe, Yuta; Imabayashi, Tatsuya; Yamada, Takahiro; Okada, Satoru; Shimamoto, Takayuki; Chihara, Yusuke; Iwasaku, Masahiro; Kaneko, Yoshiko; Uchino, Junichi; Inoue, Masayoshi; Konishi, Eiichi; Takayama, K.

doi:10.1016/j.lungcan.2019.09.012

Cited by 11 publications

(12 citation statements)

References 30 publications

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“…Using two recently published meta-analyses (18,19), we reviewed the prevalence of PD-L1 expression in studies using FDA-approved PD-L1 assays in SCLC, which were the same as those used in our study, for a more accurate comparison (Table 3). A total of eight studies used SP142 and/or 22C3 PD-L1 assays (7,(25)(26)(27)(28)(29)(30)(31); only one study used the SP263 assay (7). As seen in Table 3 showing our results, the prevalence of PD-L1 expression did not show large difference as they did in the meta-analysis and was lower compared to what has been reported for NSCLC (14,16,19).…”

Section: Discussionmentioning

confidence: 44%

“…ICIs targeting the signaling of programmed death 1 (PD-1) or its ligand 1 (PD-L1) have shown promising responses in some patients with advanced non-small cell lung cancer (NSCLC) (4)(5)(6). However, the clinical response rate of PD-1/PD-L1 inhibitors against several solid tumors, including lung cancer, is only approximately 20% (4,6,7). Thus, predictive biomarkers represnet an unmet need to identify patients who may clinically benefit from PD-1/PD-L1 inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

Lee

Lim

Ryu

et al. 2021

Transl Lung Cancer Res

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Background: Evidence of the clinical impact of programmed death-ligand 1 (PD-L1) expression in small cell lung cancer (SCLC) is scarce and conflicting, even though atezolizumab became the first PD-L1 inhibitor approved by the US Food and Drug Administration (FDA) in recent years for the initial treatment of extensive-stage (ES)-SCLC.Methods: We investigated PD-L1 expression in SCLC tumors using the three validated PD-L1 immunohistochemistry (IHC) assays (SP263, SP142, and 22C3) and assessed the correlation between PD-L1 expression and clinicopathological factors to determine the prognostic value of PD-L1 expression. The three PD-L1 IHC analyses were prospectively used to assess tumor samples of patients with SCLC at diagnosis.Results: Of the total of 59 patients, 47 patients received the active treatment beyond platinum-based chemotherapy at our institution. PD-L1 expression was positive in 39.0% with SP263, 37.3% with SP142, and 22.0% with 22C3. In a univariate analysis, the positive result of at least one of the three PD-L1 assays and the positive result of the SP142 assay were associated with longer overall survival (OS). A multivariable analysis confirmed that performance status, stage, and the SP142 assay were independent predictors of OS.In subgroup analysis, these results revealed more significant prognostic factors in ES than in limited-stage (LS). In patients with SCLC, especially those with ES, the expression of the SP142 assay is a significant independent prognostic factor.Conclusions: Although these results need to be further validated in larger cohorts, this information will benefit clinicians and patients in determining the immunotherapy for patients with ES-SCLC.

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Section: Discussionmentioning

confidence: 44%

Section: Introductionmentioning

confidence: 99%

The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

Lee

Lim

Ryu

et al. 2021

Transl Lung Cancer Res

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“…Moreover, SCLC, unlike NSCLC and malignant melanoma, is generally characterized by a lower rate of PD-L1 expression [29]; however, the association between PD-L1 incidence and ICI efficacy has not been determined in SCLC. Nonetheless, TMBs are reportedly associated with the efficacy of ICIs in CheckMate026 trial [5].…”

Section: Effects On Sclcmentioning

confidence: 99%

Immune Checkpoint Inhibitors for Lung Cancer Treatment: A Review

Onoi

Chihara

Uchino

et al. 2020

JCM

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132

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The treatment of lung cancer has changed drastically in recent years owing to the advent of immune checkpoint inhibitors (ICIs). A 1992 study reported that programmed cell death-1 (PD-1), an immune checkpoint molecule, is upregulated during the induction of T cell death. Since then, various immunoregulatory mechanisms involving PD-1 have been clarified, and the successful use of PD-1 blockers in anticancer therapy eventually led to the development of the current generation of ICIs. Nivolumab was the first ICI approved for treating lung cancer in 2014. Since then, various ICIs such as pembrolizumab, atezolizumab, and durvalumab have been successively introduced into clinical medicine and have shown remarkable efficacy. The introduction of ICIs constituted a major advancement in lung cancer treatment, but disease prognosis continues to remain low. Therefore, new molecular-targeted therapies coupled with existing anticancer drugs and radiotherapy have recently been explored. This review encompasses the current status, challenges, and future perspectives of ICI treatment in lung cancer.

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“…However, the concordance rate between matched specimens from SCLC patients was 89.5%, higher than that in the context of specimens from NSCLC patients (74.0%). Previous studies using the anti-PD-L1 clones 28-8, E1L3N, SP263, and 22C3 showed relatively low PD-L1 expression levels in SCLC specimens (5.0-25.0%) [22][23][24][25][26][27] compared with those in NSCLC specimens (66.0%) [19]. Bonanno et al [22] analyzed the PD-L1 expression levels in 104 SCLC patients using the 22C3 clone and reported that the number of PD-L1-positive cases was significantly higher in stage I-III versus metastatic patients (32% vs. 13%).…”

Section: Discussionmentioning

confidence: 94%

“…Of note, these studies were based on a small number of specimens and did not use the 22C3 anti-PD-L1 antibody, which is widely used for the support of ICI-based treatment decisions (such as those in the context of pembrolizumab treatment) [3,4,[19][20][21]. SCLC patients have a low positive rate of PD-L1 expression [22][23][24][25][26][27], and little is known about the concordance rate of the PD-L1 expression between EBUS-TBNA and matched TBB specimens obtained from the same patient, in the context of both SCLC and NSCLC. Therefore, confirming the suitability of EBUS-TBNA specimens for PD-L1-based ICI treatment will both impact patient outcomes and avoid the negative effects associated with invasive diagnostics and ineffective therapies.…”

Section: Introductionmentioning

confidence: 99%

Suitability of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration versus Paired Transbronchial Biopsy Specimens for Evaluating Programmed Death Ligand-1 Expression in Stage III and IV Lung Cancer: A Comparative Retrospective Study

Matsuoka¹,

Araya²,

Kita³

et al. 2021

J. Cancer

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Objectives: Cancer cells usually escape tumor-reactive T-cell responses using immune checkpoint proteins, such as programmed death protein-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1). These proteins can be blocked by immune checkpoint inhibitors (ICIs); the decision on ICI-based first-line treatment for advanced lung cancers depends on the PD-L1 levels in tumor specimens. Determining the PD-L1 expression conventionally requires histological specimens from resected tumors and core biopsy specimens. Non-small cell lung cancer (NSCLC) is usually diagnosed at stage III or IV; therefore, only small biopsy specimens, such as those obtained via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are available. However, the suitability of EBUS-TBNA specimens determining the PD-L1 expression levels in advanced lung cancers remains unclear. Materials and Methods: Here, we investigated the concordance rate of PD-L1 expression between EBUS-TBNA and matched transbronchial biopsy (TBB) specimens. Using the 22C3 anti-PD-L1 antibody (immunohistochemistry), we determined the PD-L1 expression levels in paired specimens obtained from 69 patients (50 with advanced NSCLC and 19 with small cell lung cancer [SCLC]), as well as the efficacy of ICIs in these patients. Results: The concordance rate of PD-L1 expression between the EBUS-TBNA and TBB specimens was 78.3%. The κ values referent to the PD-L1-positive expression rate between EBUS-TBNA and TBB specimens were 0.707 and 0.676 at cutoff limits of ≥1% and ≥50%, respectively. Among the 19 SCLC patients, 16 (84.2%) exhibited no PD-L1 expression in both EBUS-TBNA and TBB specimens. Notably, the progression-free survival of patients with ≥50% PD-L1 expression in the paired specimens who received ICI treatment was 8.3 months. Conclusion: Collectively, our results validate the use of EBUS-TBNA specimens for the determination of the PD-L1 expression levels in the context of NSCLC and SCLC.

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Comparing three different anti-PD-L1 antibodies for immunohistochemical evaluation of small cell lung cancer

Cited by 11 publications

References 30 publications

The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

Immune Checkpoint Inhibitors for Lung Cancer Treatment: A Review

Suitability of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration versus Paired Transbronchial Biopsy Specimens for Evaluating Programmed Death Ligand-1 Expression in Stage III and IV Lung Cancer: A Comparative Retrospective Study

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