Chemoradiotherapy (CRT) followed by durvalumab treatment improved prognosis in unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study aimed to evaluate whether the status of ...the immune-related tumour microenvironment (TME) at baseline associates with the efficacy.
This retrospective study evaluated immune-related TME factors, including programmed cell death ligand 1 (PD-L1) (clone: 22C3) expression on tumour cells and the density of CD8-positive tumour-infiltrating lymphocytes (TILs) at pre-CRT in patients with unresectable LA-NSCLC treated with CRT only (CRT alone group) and those treated with CRT followed by durvalumab (Durva group).
A total of 551 patients were included (N = 113 in the Durva group). Progression-free survival (PFS) in the Durva group was significantly greater than that in the CRT alone group (not reached NR vs 12.9 months; p = 0.002). In the CRT alone group, neither PD-L1 expression nor TIL status affected PFS; in contrast, in the Durva group, high density of CD8-positive TILs (TILHigh ≥100/mm2) and PD-L1-positive expression (tumour proportion score ≥1%; PD-L1+) was significantly associated with longer PFS (TIL: NR vs 9.5 months; p = 0.002; and PD-L1: NR vs 7.7 months; p = 0.003). On the other hand, in patients with epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, there was no significant difference in PFS between the groups (Durva vs CRT alone: 9.9 months vs 14.0 months; p = 0.77).
PD-L1+ and TILHigh at baseline could be predictive markers of the efficacy of CRT followed by durvalumab.
•In unresectable locally advanced-non-small-cell lung cancer (LA-NSCLC), it is unclear what patients can benefit from durvalumab.•The progression-free survival (PFS) of chemoradiation (CRT) alone did not differ as per PD-L1 expression and tumour-infiltrating lymphocytes (TIL) status.•PD-L1 expression and TIL status predicted longer PFS of CRT followed by durvalumab.•PD-L1 expression was significantly associated with TIL status in LA-NSCLC.
Ciliated muconodular papillary tumor/bronchiolar adenoma (CMPT/BA) is a recently introduced benign lung tumor. It remains unclear whether CMPT/BA is associated with a specific type of lung cancer ...(LC). We studied the clinicopathological characteristics and genetic profiles of the coexisting primary LC and CMPT/BA (LCCM) cases. We identified eight LCCM (0.4%) from the resected Stage 0–III primary LC (n = 1945). The LCCM cohort was male‐dominant (n = 8), elderly (median 72 years old), and most were smokers (n = 6). In addition to the adenocarcinoma (n = 8), we detected two squamous cell carcinomas and one small cell carcinoma—in some cases, multiple cancer. The target sequence/whole exome sequence (WES) revealed no shared mutations between CMPT/BA and LC. One exceptional case was invasive mucinous adenocarcinoma harboring an HRAS mutation (I46N, c.137T>A), but it was likely to be a single nucleotide polymorphism based on variant allele frequency (VAF). Other driver mutations in LC included EGFR (InDel, n = 2), BRAF(V600E) (n = 1), KRAS (n = 2), GNAS (n = 1), and TP53 (n = 2). BRAF(V600E) was the most frequent mutation in CMPT/BA (60%). In contrast, LC showed no specific trend in driver gene mutations. In conclusion, our study revealed differences in the gene mutation profiles of CMPT/BA and LC in coexisting cases, suggesting mostly independent clonal tumorigenesis of CMPT/BA from LC.
The efficacy of anti–programmed death receptor 1 (PD-1) therapy in patients with large cell neuroendocrine carcinoma (LCNEC) remains unclear. We investigated the outcome of anti–PD-1 therapy and its ...predictive markers by evaluating the immune-related tumor microenvironment.
We retrospectively reviewed patients with advanced LCNEC treated with systemic chemotherapy. We also evaluated PD ligand 1 (PD-L1) expression (clone: 22C3), CD8-positive tumor-infiltrating lymphocytes (TILs), and the mutational profiles.
Seventy patients were enrolled, and 13 of 70 patients received anti–PD-1 therapy. The progression-free survival (PFS) and objective response rate (ORR) of the anti–PD-1 therapy were 4.2 months and 39%, respectively. The overall survival of patients treated with anti–PD-1 therapy (n = 13) was significantly better than those treated without anti–PD-1 therapy (n = 57) (25.2 months vs 10.9 months; P = .02). Among the 13 patients treated with anti–PD-1 therapy, 10 patients (90%) had PD-L1–negative tumors. Patients with a high density of tumoral CD8-positive TILs (≥38/mm2) had a significantly better ORR and PFS than those with a low density of tumoral CD8-positive TILs (ORR: P = .02; PFS: P = .003). Additionally, all 3 patients with TP53 mutation co-occurring with PIK3CA mutation (2 of 8 patients) or RB1 mutation (1 of 8 patients) responded to anti–PD-1 therapy.
Anti–PD-1 therapy was effective regardless of PD-L1 positivity in patients with advanced LCNEC. Our investigation might suggest that the density of tumoral CD8-positive TILs and the presence of co-occurring mutations are predictors of the efficacy of anti–PD-1 therapy in patients with advanced LCNEC.
We evaluated the efficacy of anti–programmed death receptor 1 (PD-1) therapy in patients with advanced large cell neuroendocrine carcinoma (LCNEC). Anti–PD-1 therapy was effective regardless of programmed death ligand 1 (PD-L1) positivity. The density of tumoral CD8-positive tumor-infiltrating lymphocytes and the presence of co-occurring mutations might be predictors of the efficacy of anti–PD-1 therapy in patients with advanced LCNEC.
Highlights • First report of successful desensitization against skin rash induced by alectinib. • The patient was able to resume alectinib treatment safely after desensitization. • Desensitization ...should be considered in patients with alectinib sensitivities.
Pembrolizumab is the standard first‐line treatment for advanced non‐small cell lung cancer (NSCLC) with programmed death‐ligand 1 (PD‐L1) expression tumor proportion score (TPS) ≥50%. The benefit of ...pembrolizumab in patients with advanced NSCLC and poor performance status (PS ≥3) is limited, even when the tumor is PD‐L1‐expression‐positive. We retrospectively reviewed a total of four NSCLC cases with high PD‐L1 expression (TPS ≥50%) and poor PS. The only patient with very high PD‐L1 expression (TPS 100%) responded to pembrolizumab, but none of the three patients with high PD‐L1 expression (50%–80%) responded to pembrolizumab. In conclusion, pembrolizumab can serve as a treatment option for patients with poor PS, if PD‐L1 expression TPS is 100%.
Pembrolizumab may be a treatment option in patients with poor PS, if TPS of PD‐L1 on tumor cells are 100%.
Pemetrexed monotherapy has come to be recognized as the standard of care for second-line therapy of non-squamous non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) expression is recognized ...as a potential predictor of the response to pemetrexed-based chemotherapy in patients with advanced NSCLC. The purpose of this study was to identify useful predictors of the response to pemetrexed other than TS expression.
The records of non-squamous NSCLC patients without driver mutations who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2009 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated.
In the 116 patients with non-squamous NSCLC, the overall response rate and progression-free survival (PFS) were 10.3% and 2.1 months, respectively. The disease control rate and PFS differed significantly among current smokers and never-smokers/former light smokers (44.9 vs. 65.8%, and 1.8 vs. 4.0 months, respectively). Furthermore, multivariate analysis identified Eastern Cooperative Oncology Group Performance Status and smoking status as independent predictors of the PFS.
The clinical data obtained in this study may provide a valuable basis for the use of smoking status as a predictor of pemetrexed monotherapy in wild-type NSCLC patients.
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Background: Pembrolizumab and atezolizumab monotherapy has been the standard of care in treatment-naïve advanced NSCLC with high PD-L1 expression. On the other hand, the evaluation of PD-L1 ...expression as companion diagnostics is different between two agents (Clone: 22C3 and SP142). PD-L1 Immunohistochemistry Comparability Study showed that the SP142 assay showed significantly less sensitivity to detect PD-L1 expression on TCs, leading to the discrepancy in cases with PD-L1 high expression on tumor cells (TCs). This study aimed to evaluate the clinical impact of the discrepancy in PD-L1 high expression on the efficacy of pembrolizumab monotherapy in advanced NSCLC patients. Methods: We retrospectively reviewed advanced NSCLC patients with PD-L1 high expression (22C3: TPS ≥ 50%) who received first-line pembrolizumab monotherapy, and had sufficient tumor tissues for evaluating PD-L1 expression on TCs (SP142). Additionally, RNA-sequence analysis was performed to evaluate the biological differences in the discrepancy cases with PD-L1 high expression on TCs. Results: A total of 45 patients (PD-L1 expression TPS 22C3: ≥ 50%) were included. Of these patients, 5 / 9 / 18 / 13 patients had PD-L1 expression (SP142): TC 0 / 1 / 2 / 3, respectively. The objective response rate (ORR) and median PFS (mPFS) of pembrolizumab in all pts were 62% (95% confidence interval CI, 47-76) and 7.52 months (mo, 95% CI, 4.73-10.97). The ORR and PFS in patients with TC ≤ 1 were significantly worse than those with TC ≥ 2 (TC ≤ 1 vs. TC ≥ 2: ORR 21% vs. 81%, p < 0.001, and mPFS 3.81 mo vs. 8.05 mo, p = 0.004, Table). In patients with PD-L1 TPS ≥ 90% (n = 34), the ORR and PFS in patients with TC ≤ 1 were also significantly worse than those with TC ≥ 2 (TC ≤ 1 vs TC ≥ 2: ORR 0% vs. 82%, p < 0.001, and mPFS 2.04 mo vs. 10.97 mo, p < 0.001, Table). Additionally, RNA-sequence analysis showed that tumors with TC ≤ 1 had significantly suppressed immune-related pathways (ALLOGRAFT REJECTION and IFNG RESPONSE) and significantly lower T-cell-inflamed gene expression profiles compared with those with TC ≥ 2. Conclusions: Discrepancy in PD-L1 expression on tumor cells between 22C3 and SP142 assay was a negative predictive factor for pembrolizumab monotherapy and showed suppressed tumor microenvironment.Table: see text
Small cell lung cancer (SCLC) is typically categorized according to disease extent as limited or extensive, and utility of the 8th TNM classification, recommended for lung cancer staging, which ...demonstrates a strong association with non-small-cell lung cancer (NSCLC) management, remains unclear.
This retrospective study included 277 consecutive SCLC patients treated at a single institution between 2008 and 2016.
According to the currently used two-stage system, 186 (65.7%) of the patients were classified as having extensive disease (ED)-SCLC. Among the ED-SCLC patients, ten (5.3%), 38 (20.4%), 32 (17.2%), and 106 (57.0%) were categorized into stages M0, M1a, M1b, and M1c, respectively, according to the 8th TNM classification. There was a significant difference in overall survival based on the M descriptors: 15.8 (95% CI 9.4-22.2) months in the M1b group vs 7.3 (95% CI 5.7-8.9) months in the M1c group (
<0.001). Multivariate analysis showed that in addition to the known prognostic factors such as performance status, serum albumin, and lactate dehydrogenase, M descriptor was a prognostic factor (HR 1.95, 95% CI 1.38-2.77;
<0.001).
The 8th TNM classification has a prognostic value in SCLC. Similarly to NSCLC, treatment approaches should be considered on the basis of the 8th TNM classification, especially stage IVA separate from stage IVB in ED-SCLC patients.
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