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  • American Society of Clinical Oncology (ASCO)  (4)
  • 1
    Online Resource
    Online Resource
    Phase I/II study of depatuxizumab mafodotin (ABT-414) monotherapy or combination with temozolomide in Japanese patients with/without EGFR -amplified recurrent glioblastoma.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 2065-2065
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 2065-2065
    Abstract: 2065 Background: The poor prognosis of glioblastoma (GBM; WHO grade IV) results from a high rate of disease recurrence and lack of effective treatment options. Depatuxizumab mafodotin (depatux-m, ABT-414) is comprised of an EGFR-directed antibody, depatuxizumab (depatux, ABT-806), conjugated to the microtubule toxin monomethyl auristatin F (MMAF, mafodotin). Once bounded with tumor cells, depatux-m is internalized and releases the cytotoxin, resulting in cell death. Here, we report safety, pharmacokinetic (PK) and efficacy in an ongoing phase 1/2 study of Japanese patients with/without EGFR-amplified recurrent GBM (rGBM). Methods: M13-714 (INTELLANCE-J, NCT02590263) is a non-randomized, phase 1/2 study in Japanese patients. Phase 1 assessed tolerability and PK where the dose escalation of depatux-m was from 0.5 to 1.25 mg/kg/Q2W at day 1 and 15 during 28-day cycle until progression disease (PD) or intolerable toxicity. Phase 2 assessed efficacy and safety of depatux-m in EGFR-amplified, rGBM and patients received 1.0 mg/kg of depatux-m on day 1 and 15 + 150 mg/m 2 temozolomide (TMZ) on days 1-5 during each 28-day cycle until PD or intolerable toxicity. Results: As of 10 Jan 2019, 38 patients (WHO grade ≥3) were enrolled (9 in phase 1, 29 in phase 2). There was no dose limiting toxicity in phase 1. The recommended phase 2 dose was 1.25 mg/kg where the most common adverse events (AEs) were punctate keratitis in 21 patients (72%); lymphopenia in 14 patients (45%), thrombocytopenia in 13 patients (41%). Grade 3/4 AEs included thrombocytopenia and lymphopenia in 20 patients (69%). Ocular AEs were reported in 27 patients (93%) including punctate keratitis (72%). PK results (31 patients) in both phases were similar to those of non-Japanese result. Progression Free Survival (PFS) of 27 patients in phase 2 for 12 and 6 months were 8% and 27.5% respectively. The median PFS was 4 months. The overall survival (OS) for 24, 12 and 6 months were 28%, 62.5% and 93% respectively. The median OS was 15.5 months. Conclusions: Preliminary safety, PK and efficacy in Japanese patients with/without EGFR-amplified, rGBM suggests depatux-m was tolerated and showed encouraging anti-GBM effects. Clinical trial information: NCT02590263.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.2065
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Cytokeratin 19 fragment (CYFRA21-1) to predict the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) harboring EGFR mutation.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 10610-10610
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 10610-10610
    Abstract: 10610 Background: EGFR mutation is independently associated with a favorable response in NSCLC patients receiving EGFR-TKIs, regardless of gender or smoking history. However, recent reports have indicated that squamous cell carcinoma patients harboring EGFR mutations show a worse response to EGFR-TKIs than adenocarcinoma patients. We hypothesized that serum CYFRA21-1 is a predictive marker in EGFR mutated patients treated with EGFR-TKIs. Methods: We retrospectively screened 160 NSCLC patients harboring EGFR mutations (exon 19 deletions, L858R in exon 21, or other minor mutations) who received either gefitinib or erlotinib between 1992 and 2011. Patients were screened for histology, sex, age, smoking status, efficacy of EGFR-TKI and tumor markers (CEA/CYFRA21-1) at initial diagnosis. Results: Out of 160 eligible patients treated with EGFR-TKIs, 77 patients with high CYFRA21-1 level ( 〉 2 ng/ml) showed statistically shorter progression-free survival (PFS) than 83 patients with normal CYFRA21-1 level (median PFS 7.5 vs 14.0 months, p=0.006). No significant difference in PFS was observed between high CEA group ( 〉 5 ng/ml) and normal CEA group (median PFS 8.6 vs 11.2 months, p=0.2423). Multivariate analysis revealed that high CYFRA21-1 level is independently associated with PFS (HR 1.35; p=0.002) as well as squamous cell carcinoma (HR 1.40; p=0.020) and performance status 2-4 (HR 2.63; p=0.003). No statistically significant difference in overall survival (OS) was observed between high CYFRA21-1 group and normal group (median OS 24.8 vs 39.1 months, p=0.104). Conclusions: High CYFRA level patients have significantly shorter PFS, which may indicate that this subgroup has a larger squamous component and thus less response to EGFR-TKIs. Serum CYFRA21-1 level is a predictive marker of EGFR-TKIs efficacy and EGFR mutated patients can be divided into two subgroups according to CYFRA21-1 level at initial diagnosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.10610
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Rebiopsy of non-small cell lung cancer patients with acquired resistance to EGFR-TKI: Comparison between T790M mutation-positive and -negative populations.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 7528-7528
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 7528-7528
    Abstract: 7528 Background: The secondary epidermal growth factor receptor (EGFR) mutation T790M accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitors (TKI). A recent report has demonstrated the presence of T790M predicts a favorable prognosis and indolent progression, compared to the absence of T790M after TKI failure. However, rebiopsy to confirm T790M status can be challenging due to limited tissue availability and procedural feasibility, and little is known regarding the differences among patients with or without T790M. Methods: We investigated 73 patients harboring EGFR sensitive mutations who had undergone rebiopsy to confirm the emergence of T790M after TKI failure. The peptide nucleic acid-locked nucleic acid PCR clamp method was used in EGFR mutational analyses. Patient characteristics (age, gender, smoking history, performance status, EGFR mutation site, initial TKI, response to initial TKI, line of initial TKI, progression-free survival with initial TKI, and biopsy site) and postprogression survivals (PPS) after initial TKI failure, were retrospectively compared in patients with and without T790M. Results: We identified T790M in 2 (10%) of 21 central nervous system (CNS) (19 cerebrospinal fluid and 2 brain tissue) specimens, and in 20 (38%) of 52 other lesions (25 lung tissue, 24 pleural effusion, and 3 lymph node) (p = 0.0225). Other characteristics had no statistical association with the detection of T790M. Median PPS in patients with T790M was 34.0 months, and in those without T790M, 14.5 months (p = 0.0038). Although none of our patients received TKIs continuously after initial failure, 56 (77%) patients were re-administered TKIs. Regardless of T790M status, PPS in patients with TKI re-administration (23.4 months) was significantly longer than without re-administration (10.4 months) (p = 0.0085). Conclusions: The emergence of T790M in CNS is rare compared with other lesions. Patients with T790M after TKI failure have significantly better prognosis than those without T790M. The effectiveness of TKI re-administration or continuous administration beyond progression is suggested after initial TKI failure.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.7528
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 4
    Online Resource
    Online Resource
    High-dose erlotinib for refractory leptomeningeal metastases (LM) after failure of standard dose EGFR-TKIs.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 8098-8098
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 8098-8098
    Abstract: 8098 Background: EGFR-TKIs, gefitinib and erlotinib can demonstrate dramatic and durable response in patients with EGFR-mutant non-small cell lung cancer. Approximately one-third of patients develop central nervous system (CNS) metastases, including leptomeningeal metastases (LM) after initial response to EGFR-TKIs. Pharmacokinetic failure due to insufficient penetration of EGFR-TKIs is suggested as a cause of CNS failure. Therefore, high-dose EGFR-TKIs are considered reasonable therapeutic options for refractory CNS metastases after failure of standard dose EGFR-TKIs, but there is little present evidence of high-dose EGFR-TKI’s efficacy and tolerability. Methods: Between 2007 and 2012, we screened 279 patients harboring EGFR sensitive mutations, and identified 31 patients with LM. Ten of 31 patients received high-dose erlotinib, and the other 21 underwent only standard dose EGFR-TKIs (gefitinib and/or erlotinib). In these 10 patients, erlotinib was administered at 200 mg on alternating days (n=2), 300 mg on alternating days (n=6), 300 mg every 3 days (n=1), or 600 mg every 4 days (n=1). We retrospectively investigated the efficacy and tolerability of high-dose erlotinib. Additionally, survivals from the diagnosis of LM to death were compared in patients with or without high-dose erlotinib. Results: Regarding high-dose erlotinib, five of 10 patients were radiologically evaluable, and partial response was observed in 60% (3/5), stable disease in 20% (1/5), and progressive diasease 20% (1/5). Median time to CNS progression was 3.4 months (range, 0.3-6.6 months). Improvement of neurological symptoms was observed in 9 (90%) of 10 patients. No severe adverse events (≥ grade 3) associated with high-dose erlotinib were confirmed. Median survival from the diagnosis of LM in patients with high-dose erlotinib was 6.5 months (95% CI: 2.5-12.3 months), and that in those without was 5.8 months (95% CI: 1.1-7.8 months) (p =0.51). Conclusions: The efficacy and tolerability of high-dose erlotinib were suggested for refractory LM. It can be a therapeutic option in patients after failure of standard dose erlotinib. Optimal dose and schedule are unclear, and further investigations are warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.8098
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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