Dataset Information

The efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer harboring driver mutations.

ABSTRACT: The present retrospective study was conducted to evaluate the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) harboring driver mutations. Patients with NSCLC harboring driver mutations who received ICIs (nivolumab or pembrolizumab) were reviewed in Hirosaki University and Aomori Prefectural Central Hospital. There were 139 patients who received molecular targeted drugs, including 24 patients treated with ICIs. Patient characteristics were as follows: Male/female, 5/19; median age 68 (range 39-82); smoking/non-smoking, 6/18; PS 0-1/2, 20/4; driver mutation status, EGFR/ALK/RET/ROS1: 21/1/1/1. The overall response rate was 16.7% [95% confidence interval (CI), 7.0-37.1%] and the disease control rate was 33.4% (95% CI, 18.9-55.1%). The median progression-free survival (PFS) time was 62 days (95% CI 52-81 days). In the patients who had been treated by the preceding tyrosine kinase inhibitor (TKI) for >1 year, the PFS time was 110 days. On the other hand, in the patients who had received a TKI for less than a year, the PFS time was 56 days, which was significantly shorter (P=0.012). To conclude, some of the patients with NSCLC harboring driver mutation could benefit from ICIs, and the duration of previous TKI treatment may be associated with the efficacy.

SUBMITTER: Sakamoto H

PROVIDER: S-EPMC6482391 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer harboring driver mutations.

Sakamoto Hiroaki H Tanaka Hisashi H Shiratori Toshihiro T Baba Keisuke K Ishioka Yoshiko Y Itoga Masamichi M Taima Kageaki K Hasegawa Yukihiro Y Takanashi Shingo S Tasaka Sadatomo S

Molecular and clinical oncology 20190403 6

The present retrospective study was conducted to evaluate the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) harboring driver mutations. Patients with NSCLC harboring driver mutations who received ICIs (nivolumab or pembrolizumab) were reviewed in Hirosaki University and Aomori Prefectural Central Hospital. There were 139 patients who received molecular targeted drugs, including 24 patients treated with ICIs. Patient characteristics w ...[more]

PMID: 31031976

Similar Datasets

Project description:BackgroundKirsten rat sarcoma homolog (KRAS) mutations are one of the key drivers in non-small cell lung cancer (NSCLC) and FDA-approved specific inhibitors of KRAS-G12C mutation are available clinically. However, inhibitors of certain KRAS mutation subtypes remain unavailable, especially rare KRAS mutations including G13C, G13D, and Q61H. In this study, we retrospectively investigated the outcomes of NSCLC patients with rare KRAS-mutation to determine if they may benefit from immune checkpoint inhibitors (ICIs).MethodsOur retrospective study involved 240 advanced NSCLC patients with KRAS mutations, who visited Shanghai Chest Hospital from July 2018 to July 2021. Complete clinical and pathological data were recorded and progression-free survival (PFS) and overall survival (OS) were adopted as primary endpoints.ResultsThe median follow-up time was 36.5 months (range, 30.8-42.1 months) and the median OS was 9.7 months (range, 7.6-11.8 months). Of the 240 patients evaluated, 130 (54.2%) received chemotherapy and 110 (45.8%) received ICI-based treatment. Among the patients who received chemotherapy, patients with rare KRAS-mutations presented worse survival outcomes (median PFS, 3.4 vs. 4.1 months, P=0.047; median OS, 5.2 vs. 7.1 months, P=0.02) than conventional KRAS-mutant patients. PFS and OS of rare KRAS-mutation patients were prolonged after immunotherapy (median PFS 7.3 vs. 3.4 months, P<0.001; median OS, 13.3 vs. 5.2 months, P<0.001) and had no significant difference compared with conventional KRAS-mutant patients, in part of them whose programmed death-ligand 1 (PD-L1) expression data before immunotherapy were available (n=72), patients with a higher rate of PD-L1 positive tumor cells (≥50%) presented elevated PFS and OS.ConclusionsDespite having potential survival disadvantage compared with other NSCLC patients, rare KRAS-mutant patients (other than G12A, C, D, V) could benefit specifically from ICI-based therapy and survival outcomes are correlated with PD-L1 expression.

Project description:BackgroundAlthough predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been suggested by several studies, their assessments were insufficient because patients were categorized only by the occurrence of irAEs. It has not been elucidated whether irAEs also play a significant role even in responders.Materials and methodsBetween December 2015 and September 2018, 106 patients with advanced non-small cell lung cancer treated with ICIs were enrolled in our prospective biomarker study. Twenty-three of these were responders, defined as those with complete or partial response. We investigated the proportion of irAEs among overall and responders. For responders, progression-free survival (PFS) and overall survival of ICIs were compared between those with and without irAEs. As an exploratory analysis, we measured 41 proteins from peripheral blood before and after ICI treatment.ResultsThe proportion of irAEs was significantly higher in responders than nonresponders (65.2% vs. 19.3%, p < .01). Among responders, clinical characteristics did not differ regardless of the occurrence of irAEs. However, there was a significant difference in PFS among responders (irAE group 19.1 months vs. non-irAE group 5.6 months; hazard ratio: 0.30 [95% confidence interval: 0.10-0.85]; p = .02). Of 41 protein analyses, fibroblast growth factor-2 at baseline and monocyte chemoattractant protein fold change showed significant differences between them (p < .04).ConclusionAlthough this is a small sample-sized study, irAE might be a predictive factor of durable efficacy, even in patients who responded to ICIs. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.Implications for practiceAlthough the predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) has been suggested by several studies, it has not been elucidated whether irAEs also play a significant role even in responders. This study showed that more than 60% of responders had irAEs. It demonstrated the strong correlation between irAEs and efficacy even in responders. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have witnessed the achievements of convincing clinical benefits that feature the significantly prolonged overall survival (OS) of patients suffering from advanced non-small cell lung cancer (NSCLC), according to reports recently. Sensitivity to immunotherapy is related to several biomarkers, such as PD-L1 expression, TMB level, MSI-H and MMR. However, a further investigation into the novel biomarkers of the prognosis on ICIs treatment is required. In addition, there is an urgent demand for the establishment of a systematic hazard model to assess the efficacy of ICIs therapy for advanced NSCLC patients.MethodsIn this study, the gene mutation and clinical data of NSCLC patients was obtained from the TCGA database, followed by the analysis of the detailed clinical information and mutational data relating to two advanced NSCLC cohorts receiving the ICIs treatment from the cBioPortal of Cancer Genomics. The Kaplan-Meier plot method was used to perform survival analyses, while selected variables were adopted to develop a systematic nomogram. The prognostic significance of ERBB4 in pan-cancer was analyzed by another cohort from the cBioPortal of Cancer Genomics.ResultsThe mutation frequencies of TP53 and ERBB4 were 54% and 8% in NSCLC, respectively. The mutual exclusive analysis in cBioPortal has indicated that ERBB4 does show co-occurencing mutations with TP53. Patients with ERBB4 mutations were confirmed to have better prognosis for ICIs treatment, compared to those seeing ERBB4 wild type (PFS: exact p = 0.017; OS: exact p < 0.01) and only TP53 mutations (OS: p = 0.021). The mutation status of ERBB4 and TP53 was tightly linked to DCB of ICIs treatment, PD-L1 expression, TMB value, and TIICs. Finally, a novel nomogram was built to evaluate the efficacy of ICIs therapy.ConclusionERBB4 mutations could serve as a predictive biomarker for the prognosis of ICIs treatment. The systematic nomogram was proven to have the great potential for evaluating the efficacy of ICIs therapy for advanced NSCLC patients.

Project description:BackgroundResponse to immune checkpoint inhibitors (ICIs) is affected by multiple factors. This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer (NSCLC) patients.MethodsThe data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People's Hospital between May 2019 and July 2020 were retrospectively analyzed. Metastatic sites included liver, bone, brain, adrenal gland, pleura, and contralateral lung. Progression-free survival (PFS) and overall survival (OS) were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method. Organ-specific disease control rate (OSDCR) of different individual metastatic sites was evaluated.ResultsForty NSCLC patients meeting the criteria were identified. The presence of liver metastasis was significantly associated with shorter PFS (3.1 vs . 15.5 months, P = 0.0005) and OS (11.1 months vs . not reached, P = 0.0016). Besides, patients with bone metastasis tend to get shorter PFS (4.2 vs . 15.5 months, P = 0.0532) rather than OS ( P = 0.6086). Moreover, the application of local treatment could numerically prolong PFS in patients with brain metastasis (15.5 vs . 4.3 months, P = 0.1894). More metastatic organs involved were associated with inferior PFS ( P = 0.0052) but not OS ( P = 0.0791). The presence of liver metastasis or bone metastasis was associated with more metastatic organs (Phi[ϕ]: 0.516, P = 0.001). The highest OSDCR was observed in lung (15/17), and the lowest in the liver (1/4).ConclusionsMetastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC. ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis, thus patients with this type of metastasis might require more aggressive combination strategies.

Dataset Information

The efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer harboring driver mutations.

Publications

The efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer harboring driver mutations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets