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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 2030-2030
    Abstract: 2030 Background: Renal cancer is the fourth most common cause of metastatic tumors to the brain. Tyrosine kinase inhibitors (TKIs) targeting VEGFR and other receptors, such as sunitinib, pazopanib, etc., have been used as first line for renal cell carcinoma brain metastasis (RCCBM). Immune Checkpoint Inhibitors (ICIs) targeting PD-L1 and CTLA-4 interactions, such as nivolumab and ipilimumab respectively, have also been used as first line treatment for RCCBM. However, the efficacy of TKIs alone, ICIs alone, or TKIs and ICIs combined as first line treatment has emerged as a topic of interest. Methods: Patients with RCCBM treated with either TKIs, ICIs, or both at our tertiary care center from 2010-2019 were evaluated. Overall Survival (OS) was measured from initiation of either TKI or ICI therapy to date of death or last follow up. The Cox proportional hazard model was used to determine differences in OS. Results: 218 patients with RCCBM were included. Of these, 32 were treated with ICIs alone, 112 were treated with TKIs alone, and 76 were treated with a combination of ICIs and TKIs. For ICI treatment alone the median age at diagnosis was 61 years (Interquartile range (IQR) 38-82), 72% of the patients were male, and 97% were white. For TKI treatment alone the median age at diagnosis was 58 years (IQR 37-82), 70% of the patients were male, and 92% were white. For the combination cohort the median age at diagnosis was 63 years (IQR 45-79), 69% of the patients were male, and 97% were white. OS for patients receiving ICI, TKI, and combination treatment had a median of 69.1, 42.7, and 126.0 months and a 2-year rate of 77%, 69%, and 93%, respectively. With ICI treatment as a reference, TKI treated patients had an OS hazard ratio of 1.32 (95% CI = 0.78 - 2.21, p = 0.30) and ICI/TKI combination had an OS hazard ratio of 0.52 (95% CI = 0.30 - 0.92, p = 0.024). Conclusions: A combination treatment of ICIs and TKIs was associated with an increase in OS when compared to treatment with either TKIs or ICIs alone in patients with RCCBM. These results should be interpreted cautiously due to treatment selection bias. Further studies need to be done to control for other patient variables such as performance status, number of intracranial lesions, and extra-cranial metastasis.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e14009-e14009
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e14009-e14009
    Abstract: e14009 Background: Breast cancer is the second most common cause of metastatic brain tumors. The presence of estrogen receptors (ER), and progesterone receptors (PR), and HER2 receptors have been used to guide both hormonal and targeted therapies for breast cancer. The presence or absence of these receptors may impact patient outcomes in breast cancer brain metastasis (BCBM). Methods: Patients with BCBM and known tumor marker status treated at our tertiary care center from 2010-2019 were evaluated. Overall Survival (OS) was measured from diagnosis of BCBM to date of death or last follow up. Many of these patients received multiple lines of treatment including hormonal and targeted therapies at some point during their care. The Cox proportional hazard model was used to determine differences in OS. Results: 137 patients with BCBM were included. Of these, 48 were ER or ER/PR positive (ER+), 3 were PR positive (PR+), and 47 were HER2, HER2/PR, HER2/ER, or HER2/ER/PR positive (HER2+), and 37 were triple-negative. For ER+ tumors the median age at diagnosis was 60 years (Interquartile range (IQR) 31-87) and 86% were white. For PR+ tumors the median age at diagnosis was 67 years (IQR 66-74) and 75% were white. For HER2+ tumors the median age at diagnosis was 55 years (IQR 31-84) and 79% were white. For triple-negative tumors the median age at diagnosis was 56 years (IQR 34-91) and 83% were white. OS for ER+, PR+, HER2+, and triple-negative patients had a median of 57.7, 19.8, 137.4, and 54.6 months and a 2-year rate of 76%, 33%, 82%, and 73%, respectively. With ER+ patients as a reference, PR+ patients had an OS hazard ratio of 1.49 (95% CI = 0.35 - 6.23, p = 0.59), HER2+ patients had an OS hazard ratio of 0.62 (95% CI = 0.36 - 1.06, p = 0.082), and triple-negative patients had an OS hazard ratio of 0.92 (95% CI = 0.54 - 1.57, p = 0.77). Conclusions: HER2+ tumors were associated with an increase in OS when compared to ER+, PR+, and triple-negative tumors in patients with BCBM. The OS of the other three tumor marker groups was not significantly different from one another. Further studies need to be done within tumor marker cohorts to determine the most effective treatments within those cohorts.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 2031-2031
    Abstract: 2031 Background: Non-small cell lung cancer (NSCLC) is the most common cause of brain metastases, with 10-30% of patients developing brain metastases. EGFR is a transmembrane glycoprotein that is mutated in up to 50% of NSCLCs. First-generation EGFR tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib, are limited by blood-brain barrier (BBB) penetration and exon 20 (T790M) tumor mutations. Third-generation EGFR TKIs, such as osimertinib, have shown better BBB penetration and efficacy against T790M mutations. In this retrospective study, we evaluated the overall survival (OS) and progression-free survival (PFS) in NSCLCBM patients treated with first and third-generation EGFR TKIs. Methods: NSCLCBM patients diagnosed between 2010 and 2019 at our tertiary care center were investigated. Information regarding molecular marker status, systemic therapies, and date of progression were collected. OS was defined as the start date of systemic therapy to the date of last follow-up or death. OS and PFS were estimated by the Cox proportional model. Results: A total of 193 NSCLCBM patients with an EGFR mutation were identified. 33 EGFR mutant patients received first-generation EGFR TKIs, of which 56.7% were females, 82.1% were white, and had a median age of 63.2 years. 22 patients received third-generation EGFR TKIs, 64.1% being female, 76.9% being white, and with a median age of 71.5 years. The median OS (mOS) in patients who received first and third-generation EGFR TKIs was 59.8 months and 65.9 months respectively (p-value (p) = 0.06). The median PFS (mPFS) between the first and third-generation EGFR TKI cohorts was 44.3 months and 66.9 months respectively (p= 0.048, hazard ratio (HR) = 0.50 (95% confidence interval (CI) = 0.25, 0.99). Conclusions: Newer generation of targeted therapies in NSCLCBM have focused on overcoming previous efficacy hurdles, including BBB penetration and resistant mutations. We determined that there was a significant mPFS benefit in osimertinib compared to erlotinib or gefitinib, and a trend towards significant mOS benefit in osimertinib compared to erlotinib or gefitinib in patients with NSCLCBM. However, these results should be interpreted cautiously due to treatment selection bias, and further studies need to be conducted on brain metastases lesion size and response rates.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 2034-2034
    Abstract: 2034 Background: Non-small cell lung cancer (NSCLC) is the most common cause of brain metastases. ALK, which codes for tyrosine kinase receptors, is rearranged in 4-7% of NSCLC. First-generation ALK inhibitors have restricted efficacy due to poor blood-brain barrier (BBB) penetration and ALK-resistant tumor mutations. Second-generation ALK inhibitors have shown better BBB penetration, while third-generation ALK inhibitors were efficacious even against ALK-resistant mutations. In this retrospective study, we investigated the overall survival (OS) and progression-free survival (PFS) in NSCLCBM patients treated with first, second, and third-generation ALK inhibitors. Methods: NSCLCBM patients between 2010 and 2019 were evaluated. We analyzed data regarding molecular marker status, systemic therapies, and date of progression. OS was defined as the start date of systemic therapy to the date of last follow-up or death. The Cox proportional model was used to estimate OS and PFS. Results: A total of 90 patients had ALK gene rearrangement. 16 ALK positive patients received first-generation ALK inhibitor (crizotinib), with a median age of 59.2 years, 50% of the cohort being female and 83.3% being white. Another 17 patients received second-generation (alectinib, ceritinib, brigatinib) and third-generation ALK inhibitors (lorlatinib), with a combined median age of 52.2 years and a cohort of 52.6% females and 72.2% white patients. The 5-year OS rate was 49% (95% confidence interval (CI) = 24%, 71%) for first-generation ALK inhibitors and 76% (95% CI = 40%, 92%) for second and third-generation ALK inhibitors (p-value (p) = 0.019). The median PFS (mPFS) for patients who received first-generation ALK inhibitors was 45.3 months and for those who received second or third-generation ALK inhibitors was 180.1 months. The respective 5-year PFS rate was 43% (95% CI = 19%, 65%) and 72% (95% CI = 42%, 89%). Conclusions: Newer generations of targeted therapies in NSCLCBM have improved BBB penetration and effectiveness against resistant mutations. We determined that there was a significant 5-year OS benefit in patients who received second and third-generation ALK inhibitors compared to first-generation ALK inhibitors, and a respective trend towards significant PFS benefit in newer-generation ALK inhibitors when compared to first-generation. These results are encouraging, but the effect on intracranial lesion size and response rates should be examined in the future.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e13514-e13514
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e13514-e13514
    Abstract: e13514 Background: Half of glioblastoma (GBM) patients are 〉 65 years old (yo). We report our experience with GBM patients treated at a tertiary care center and compared outcomes in the two age groups. Methods: Half of glioblastoma (GBM) patients are 〉 65 years old (yo). We report our experience with GBM patients treated at a tertiary care center and compared outcomes in the two age groups. Results: 1165 patients were included in the final analysis. 598 patients were 〈 65 yo, and 567 were 〉 65 yo. Patients who received chemotherapy + radiation (chemoRT) had a lower risk of death compared to patients who received RT only (p 〈 0.001). Although the benefit of chemoRT seems more pronounced in patients ≥ 65 years of age [HR 0.45 (95% CI 0.36, 0.57) vs 0.61 in patients 〈 65 yo (0.48, 0.80), (p = 0.04)], the difference in effects is not significant (p = 0.07). For both MGMT-unmethylated and MGMT-methylated patients, although chemoRT had a better OS/PFS than RT only, the impact was similar in both age groups. Patients who underwent GTR or STR had a better OS/PFS than biopsy only (all p 〈 0.0001). The impact of extent of resection was not different in two age groups (all p ≥ 0.09). Patients diagnosed during 2006 – 2008 and 2009 - present had a better OS/PFS (p = 0.01 and 0.003) than those who were diagnosed during 2000-2005. The impact of diagnosis date on PFS was not different in age groups. In OS outcomes, patient diagnosed during 2009 - present had a better OS than those who were diagnosed before 2005, and the impact is more prominent for patient who were younger than 65 years (p = 0.010). Conclusions: Aggressive treatment with chemo-radiation is associated with better outcomes in both young and older GBM patients. MGMT status did not have any impact on outcomes between the two groups although MGMT status was available for only a subset of patients. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13569-e13569
    Abstract: e13569 Background: Standard post-surgical glioblastoma (GBM) treatment, per Stupp protocol, includes six-weeks of concurrent Temozolomide chemoradiation followed by at least six cycles of adjuvant-Temozolomide. Previous investigations into epidermal growth factor receptor (EGFR) amplification as a prognostic factor in GBM have yielded contradicting results, requiring further investigation. The primary aim of this study was to determine the degree to which EGFR amplification, in newly diagnosed GBM, impacted progression free survival (PFS) and overall survival (OS). Methods: Data from 582 patients who underwent surgical intervention for GBM at a tertiary care institution between 2012 and 2018 were analyzed. Only adult patients who underwent treatment per Stupp protocol and had pathological analysis on EGFR and CEP7 were included. Amplification and non-amplification status was calculated by a ratio of EGFR/CEP7 〉 2 and 〈 2, respectively. PFS and OS outcomes were compared using Cox proportional hazard models stratified by surgery type and sex. Results: Of the original 582 patients, 122 were treated per Stupp protocol and had documented EGFR analysis. Of patients who were EGFR amplified, 41 (58.5%) were male and 25 (48.1%) were female (p = 0.38) and median amplification was 1.07 and 1.16 (p 〈 0.001), respectively. EGFR non-amplified patients had a PFS hazard ratio, HR = 0.70 (95% CI = 0.44 – 1.12, p = 0.14); and an OS HR = 0.60 (95% CI = 0.35 – 1.03, p = 0.065). When the EGFR/CEP7 ratio was stratified by quartile, it was found that Q4 compared to Q1 (Q4 〉 6.50 vs 0 〈 Q1 ≤ 1.06) had a PFS HR = 2.1 (95% CI = 1.11 – 4.07, p = 0.024); and an OS HR = 2.48 (95% CI = 1.10 – 5.60, p = 0.028). Conclusions: There was no statistical difference in prevalence of EGFR amplification by sex. However, despite statistical significance, there was minimal difference in median degree of amplification by sex (0.09). Trends begin to show that patients who were EGFR non-amplified had better PFS and OS outcomes than patients who were EGFR amplified, although this was not statistically significant. Patients with very high EGFR amplification (Q4) had significantly poorer PFS and OS outcomes than patients with very low EGFR amplification (Q1).
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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