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  • American Society of Clinical Oncology (ASCO)  (3)
  • 1
    Online Resource
    Online Resource
    Nivolumab with chemotherapy in pleural mesothelioma after surgery: The NICITA trial.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS8601-TPS8601
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS8601-TPS8601
    Abstract: TPS8601 Background: Pleural mesothelioma (PM) is a highly aggressive cancer of the pleura, predominantly caused by prior asbestos exposure. Currently, there is no approved standard therapy for the treatment of early-stage PM. In most cases a multimodal therapy is recommended consisting of locoregional treatment by surgical cytoreduction via extended pleurectomy/decortication (eP/D), which, if feasible, can be combined with hyperthermic intrathoracic chemoperfusion (HITOC), together with inductive or adjuvant chemotherapy. Considering the immunogenic effects of chemotherapy on the tumor microenvironment, synergistic effects are expected when such a treatment is combined with immune checkpoint inhibitor therapy. In addition, interactions between immune infiltrates and mesothelioma cells play a role in the advent of PM, also implying a beneficial role for immunotherapy in this entity. This is also supported by recent clinical data that demonstrated beneficial effects of immune checkpoint inhibitors in patients with advanced PM. The NICITA trial is an investigator-initiated trial, investigating the combination of adjuvant chemotherapy with immune checkpoint inhibitor compared to chemotherapy alone in radically resected patients with early stage PM. Methods: The NICITA trial is a randomized, open-label, phase II clinical trial that is conducted in 14 centers across Germany. Eligible patients have been diagnosed with PM in tumor stages I-III (UICC 8 th edition) and epithelioid subtype, and must have undergone cytoreductive surgery by eP/D with or without HITOC. Patients will be randomized 1:1 to receive either a combination of 4 cycles of pemetrexed/platinum-based adjuvant chemotherapy and nivolumab (480 mg q4w) followed by nivolumab maintenance therapy (12 cycles, 480 mg q4w) or 4 cycles of adjuvant chemotherapy only. Stratification will take place according to previous HITOC treatment (yes vs. no), ECOG status (0,1 vs. 2), and achievement of macroscopic complete resection (yes vs. no). The primary endpoint of this trial is time-to-next-treatment. Secondary endpoints include additional measures of efficacy (progression-free survival, overall survival, measures of treatment-beyond-progression) and quality of life, as well as the assessment of safety. Furthermore, a comprehensive longitudinal collection of biomarker samples, including tumor tissue, blood, and stool samples, for an accompanying translational research project is implemented in this clinical trial. Sample size justification: the recruitment of 46 patients to each arm with a low drop-out rate of 13% appears feasible resulting in 40 patients to be analyzed per arm. This sample size will permit a descriptive comparison and adequately describe the tested treatment options as deduced from the precision of the median TNT confidence interval estimate. As of February 2 nd 2023, 85 of planned 92 patients have been enrolled into the NICITA trial. Clinical trial information: NCT04177953 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.TPS8601
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Blood gene expression changes in metastatic lung cancer under first-line immunotherapy according to clinical response.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e21141-e21141
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21141-e21141
    Abstract: e21141 Background: First-line pembrolizumab monotherapy is a standard treatment for metastatic non-small-cell lung cancer (NSCLC) with high PD-L1 expression (TPS ≥50%). However, many patients do not respond, and reliable biomarkers are lacking. Methods: Blood samples of 33 patients with metastatic NSCLC were analyzed at baseline (BL) and after four cycles of pembrolizumab monotherapy (FU). The expression of 12 genes involved in tumor-specific immune responses ( FAS, RORgt, FOXP3, IFNγ, FASLv1, PRF1, GATA3, PD1, CD247, GZMB, MKI67, TBX21) in whole blood RNA was quantified by RT-PCR in absolute terms using plasmids as standards. Results: Gene expression was significantly higher after immunotherapy for 11/12 genes analyzed ( FAS, RORgt, FOXP3, IFNγ, FASLv1, PRF1, GATA3, PD1, CD247, GZMB, TBX21 with fold changes [FC] 1.99 – 5.45; all p 〈 0.001). Blood neutrophil and total leukocyte counts were significantly decreased (ANC BL:7.65/nl vs. FU:5.36/nl, p = 0.024; Leu BL:10.65/nl vs. FU:7.78/nl, p = 0.032), while lymphocyte counts did not change (ALC BL:1.41/nl vs. FU:1.47/nl, p = 0.267). Increases in the expression of RORgt, FASLv1, PRF1, PD1, CD247, GZMB and TBX21 remained significant (FC 1.9 – 3.7; all p 〈 0.001) even after correction for the blood lymphocyte/leukocyte ratio (Ly/Lc BL:0.151 vs. FU:0.197, p = 0.003). Patients with long-term response (LTR, i.e. lasting 〉 6 months) had significantly higher increases in the expression of 8 genes ( RORgt, FOXP3, IFNγ, FASLv1, GATA3, PD1, CD247, TBX21) compared with patients with rapid disease progression within 3 months (RP) (FC 2.34 – 4.62, all p 〈 0.05). There were no significant differences (FU-BL) between LTR and RP regarding ANC (RP:-1.00/nl vs. LTR:-2.63/nl, p = 0.50), ALC (RP:-0,14/nl vs. LTR:+0,12/nl, p = 0,33) or Ly/Lc (RP:0.015 vs. LR:0.0542, p = 0.259). Conclusions: Pembrolizumab monotherapy of metastatic NSCLC causes significant increases in the blood expression for several genes including FAS, RORgt, FOXP3, IFNγ, FASLv1, PRF1, GATA3, PD1, CD247, GZMB, TBX21, as well as a decrease in circulating neutrophiles and total leucocytes. Long-term responders have more pronounced blood gene expression changes, which appear to correlate with long-term benefit, in contrast to blood count changes, which are not indicative. These results are currently being validated in a larger prospective study.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e21141
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Online Resource
    The impact of PD-L1 expression and co-mutations on outcome of KRAS-driven non-small-cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 9090-9090
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 9090-9090
    Abstract: 9090 Background: Interest has surged for KRAS mutated ( KRAS mut ) non-small-cell lung cancer (NSCLC) after approval of the covalent KRAS G12C inhibitors sotorasib and adagrasib. It remains unclear, how prognosis of these tumors is influenced by co-mutations and which cases could benefit most from novel drugs alongside immunotherapy (IO) or chemo-immunotherapy (CHT-IO). Methods: This retrospective study included all NSCLC patients with KRAS mut NSCLC treated in the Thoraxklinik Heidelberg from 01/2014 until 01/2021. For molecular profiling, PCR-based next-generation sequencing (NGS) was performed with a 40-gene panel, including TP53, KEAP1 and STK11. Date of progression was verified through reevaluation of radiologic images by the investigators according to RECIST v1.1. Stratification was performed according to the type of KRAS mutation (G12C vs. other), presence of TP53, STK11 and KEAP1 co-mutations ( vs. wild-type [WT] status), and the PD-L1 tumor proportion score (TPS 〈 1 aka PD-L1 neg , vs. TPS 1-49, vs. TPS 50+ aka PD-L1 high ). Results: Among 370 identified patients, no differences (all p-values 〉 0.08) were observed between KRAS G12C (n = 163) and KRAS non-G12C (n = 207) regarding clinicopathological features, like age (median 65 years), sex, smoking status, initial ECOG performance status, PD-L1 TPS, type of treatment in any line, number of treatment lines, and overall survival (OS, 19.4 months in median; details in the poster). In contrast, there was a strong association of PD-L1 TPS with OS (20.2 vs. 9.7 months for PD-L1 high vs. PD-L1 neg , p = 0.011) and progression-free survival (PFS, 5.7 vs. 1.9 months, p = 0.004) under IO. In addition, specifically within the PD-L1 neg subset, OS was longer for KRAS G12C compared to KRAS other patients (22.6 months vs. 12.1 months, p = 0.032). This was driven by the longer PFS under CHT-IO (9.7 vs. 4.5 months for KRAS G12C vs. KRAS other , p = 0.005), particularly in the absence of TP53 mutations (8.5 vs. 4.0 months with p = 0.004 for TP53 wt patients; p 〉 0.50 for TP53 mut ) and KEAP1 mutations (11.3 vs. 5.1 months with p = 0.01 for KEAP1 wt patients; p 〉 0.70 for KEAP1 mut ). Also, across all patients, KEAP1 mut cases showed a trend for shorter PFS under CHT-IO (2.7 vs. 8.0 months, p = 0.07) and IO (1.9 vs. 3.9 months, p = 0.081), as well as shorter OS (15.9 vs. 19.5 months, p = 0.068) compared to KEAP1 wt , in contrast to STK11 mut cases (p = 0.42-0.92 for the same comparisons). Overall, KRAS mut NSCLC after chemotherapy and immunotherapy showed poor prognosis under standard therapies with a median PFS of 3 months, and a median OS of 6.8 months. Conclusions: In PD-L1 neg NSCLC, KRAS G12C is associated with better outcome under CHT-IO and longer OS compared to KRAS other , especially in the absence of TP53 and KEAP1 co-mutations. KEAP1, but not STK11 mutations are associated with impaired benefit from (CHT-)IO in KRAS mut NSCLC. Treatment of KRAS mut NSCLC after chemo-immunotherapy represents an unmet medical need.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.9090
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
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