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  • American Society of Clinical Oncology (ASCO)  (3)
  • 2020-2024  (3)
  • Medicine  (3)
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  • American Society of Clinical Oncology (ASCO)  (3)
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  • 2020-2024  (3)
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  • Medicine  (3)
RVK
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 9079-9079
    Abstract: 9079 Background: EGFRm NSCLC patients (pts) have limited treatment options after EGFR-TKI failure. We previously showed that the NEJ043 study investigating ABCP in EGFRm NSCLC pts after EGFR-TKI failure had a clinically meaningful efficacy (Furuya et al, ASCO 2022). Here we report the results of the biomarker study of NEJ043. Methods: NEJ043 study is a phase II study to evaluate the efficacy of ABCP in sensitizing EGFRm nonsquamous NSCLC pts after TKI failure. Pts received atezo (1200 mg), bev (15 mg/kg), carbo (AUC 6 mg/mL/min), and pac (175 mg/m 2 ) every 3 weeks up to 4 cycles followed by atezo plus bev until loss of clinical benefit. Before treatment initiation and three cycles of ABCP, peripheral blood mononuclear cells (PBMCs) were collected, and immunophenotypic data at each time point was obtained by flow cytometry. Results: 60 pts were included in the NEJ043 study and PBMCs were obtained from 31 pts. Pts with a higher percentage of CD11b + DR low CD3 - CD14 + myeloid-derived suppressor cells (MDSCs) before ABCP had significantly longer PFS (median, 9.7 months (95% CI, 5.3-17.7) vs 5.6 months (95% CI, 3.9-8.1); HR 0.38; P = 0.0313). Further analysis of the immune cell phenotypes that changed between pre-treatment and the third course showed that pts with increased CD62L low CD8 + cells (median, 12.8 months (95% CI, 5.6-20.3) vs 5.7 months (95% CI, 4.4-8.1); HR 0.25; P = 0.003) and PD-1 + CCR7 - CD45RA - CD8 + cells (median, 8.5 months (95% CI, 5.6-13.8) vs 5.7 months (95% CI, 2.6-8.1); HR 0.37; P = 0.0324) had significantly longer PFS. Conclusions: Inhibition of MDSCs by ABCP, especially bev, may be important for EGFRm pts whose antitumor immunity is suppressed by MDSCs before treatment. Better PFS may be expected in pts in whom ABCP therapy induced CD62L low CD8 + effector T cells and PD-1 + CCR7 - CD45RA - CD8 + effector memory T cells. Clinical trial information: jRCTs031190066 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 9110-9110
    Abstract: 9110 Background: Previous studies have demonstrated poor clinical outcomes of patients (pts) with EGFRm NSCLC treated with PD-1/PD-L1 inhibitors. However, a recent subgroup analysis of the IMpower150 trial suggested the effectiveness of ABCP in NSCLC with EGFRm. The aim of this study is to further evaluate efficacy and safety of ABCP in patients with EGFRm NSCLC. Methods: This single-arm multicenter phase 2 study included pts with nonsquamous NSCLC harboring sensitizing EGFRm with prior EGFR-TKI therapy. Pts received the combination dose of atezo 1200 mg, bev 15 mg/kg, carbo AUC 6 mg/mL/min and pac 175 mg/m 2 every 3 weeks up to 4 cycles followed by atezo plus bev until loss of clinical benefit. The primary endpoint was PFS by extramural review (ER). The key secondary endpoints included OS, ORR, DoR, relative dose intensity of pac, and safety. Results: 60 pts were enrolled (median age 68 y [40–74 y], 67% were female, 55% were Ex19del and 40% were L858R). At data cutoff (November 30, 2021), median follow-up was 12.8 months in the ITT population. Median cycles of induction and maintenance therapy were 4 and 9, respectively. Median PFS was 7.4 month (95% CI, 5.7-8.2) and median OS was 18.9 month (95% CI, 13-not reached). Confirmed ORR by ER was 56% (95% CI, 43-69) and median DoR was 7.1 months (95% CI, 4.9-9.8). T790M was associated with a favorable PFS and response to the combination therapy (PFS 8.1 vs 6.8, ORR 71% vs 50%). Relative dose intensity of pac was 84%. Grade ≥3 adverse events (AEs) were reported in 92% of pts and the most common grade ≥3 AE was neutropenia (63%). Interstitial lung disease occurred in one patient (2%). AEs leading to treatment discontinuation occurred in 12% of pts. Conclusions: NEJ043 study showed that the median PFS of ABCP was 7.4 months with good tolerability. We will continue to investigate the tail plateau phenomenon of PFS and OS to conclude the clinical efficacy. Clinical trial information: 031190066.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 707-707
    Abstract: 707 Background: An oral fluoropyrimidine, S-1, is a standard adjuvant (adj) chemotherapy practice in Japan for patients (pts) with resected pancreatic cancer (PC). Patients experiencing recurrence after adj S-1 administration are treated with FOLFIRINOX (FFX), including intravenous fluoropyrimidine, or gemcitabine plus nab-paclitaxel (GN), which is commonly used as the first-line chemotherapy approach in pts with advanced PC. Some pts have good response to FFX with acceptable toxicity levels even though recurrence within 6 months (mo) after the last S-1 administration is attributed to PC refractory to fluoropyrimidine. To the best of our knowledge, there is no clinical study comparing FFX and GN in this particular population. Methods: This multi-center, retrospective study included pts with PC that had a recurrence-free interval (RFI) 〈 6 mo from the last adj S-1 administration and were treated with FFX or GN between December 2013 and 2018. The decision to administer FFX or GN was taken by the attending physicians. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response, and serious adverse events (SAE). The OS and PFS were calculated from the time of initiation of treatment with FFX or GN. To adjust confounding factors in the comparison of FFX with GN, propensity score-matching (PSM) analysis was performed. Potentially confounding factors were identified by univariate analysis for OS, and statistical significance was set at p 〈 0.1. Results: A total of 284 (FFX; 50, GN; 234) pts were enrolled from 32 institutions in Japan. Potential confounding factors comprised curability, pathological T/N, tumor differentiation status, reasons for the end of S-1 administration, chemotherapy regimen, performance status, serum albumin/C-reactive protein/carbohydrate antigen 19-9 levels, and presence or absence of liver metastasis before initiating the administration of FFX or GN. After PSM, 43 pts each in the FFX and GN groups were compared in pairs. The patient characteristics, excluding age, in the matched pair were well-balanced; the proportion of pts aged 〈 65 years in the FFX and GN groups was 61% and 30%, respectively. The median OS and PFS were longer in the GN group than in the FFX group; OS was 14.5 vs. 11.1 mo (hazard ratio [HR], 0.61; 95% confidence interval [CI] , 0.38-0.97); PFS was 7.1 vs. 5.1 mo (HR, 0.65; 95% CI, 0.41-1.02). The objective response, disease control rates, and observed SAE in the GN and FFX groups were 20/19%, 80/66%, and 14/19% respectively. Seventy-two percent of the pts in the GN group received subsequent therapies of FFX/S-1/FOLFIRI/FOLFOX (28/12/9/5%); while 77% of the FFX group pts received subsequent therapies of GN/GEM (54/7%). Conclusions: Real world data suggests that GN may be recommended in PC pts with RFI 〈 6 mo from the last administration of adj S-1.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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