Different efficacy of osimertinib in pre-TKI treated NSCLC patients with brain metastases harboring EGFR exon 19del and L858R mutant.

e21667 Background: Previous studies suggested that the efficacy of osimertinib was better in patients with epidermal growth factor receptor ( EGFR) exon 19 deletion (ex19del) than exon 21 Leu858Arg (L858R). However, the differential clinical outcomes of osimertinib in previous tyrosine kinase inhibitors (TKIs) treated non-small-cell lung cancer (NSCLC) patients with brain metastases (BrMs) according to the two different common EGFR genotypes remains undetermined. Methods: We retrospectively collected EGFR mutant (ex19del and L858R) NSCLC patients with BrMs and received osimertinib treatment between Jan 2016 and Feb 2019 in our hospital. Other eligible standards including Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, osimertinib 80mg monotherapy and neurologic symptoms existing was permitted to enroll in our study. Results: 78 patients with EGFR mutant NSCLC and BrMs were included in the study. EGFR mutation types were ex19del in 55% of patients (43/78) and L858R in 45% of patients (35/78). All of patients received at least one prior EGFR-TKI therapy, among which 46% (36/78) had gefitinib, 49% (38/78) had erlotinib, 19% (15/78) had icotinib. T790M status at osimertinib initiation was positive in 81% of patients (63/78), negative in 4% (3/78), unknown in 15% (12/78). The systemic objective response rate (ORR) was 46%. There was no apparent difference in systemic ORR (49% vs 43%, P = 0.598) between ex19del group and L858R group. The median progression free survival (PFS) and overall survival (OS) were 7.0 (range 4.7-9.3) and 18.8 (range 14.0-23.5) months for all patients. The median PFS in the ex19del and L858R subgroups was 9.1 (range 6.0-12.1) months and 5.3 (range 3.4-7.2) months, respectively ( P = 0.031). The median OS in the ex19del and L858R subgroups was 26.0 (range 13.7-38.3) months and 13.9 (range 7.7-20.2) months, respectively ( P = 0.033). Multivariate analysis identified L858R and ECOG PS 2 as poor independent predictors to the PFS and OS. Conclusions: The efficacy of osimertinib was associated with EGFR genotypes in pre-TKI treated NSCLC patients with BrMs, and L858R maybe an independent bad factor for long-term outcomes of osimertinib.

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Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis

BioMed Research International ◽

10.1155/2021/3621828 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Fangfang Lv ◽

Liang Sun ◽

Qiuping Yang ◽

Zheng Pan ◽

Yuhua Zhang

Keyword(s):

Kinase Inhibitors ◽

Meta Analysis ◽

Objective Response ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Deletion Polymorphism ◽

Asian Populations ◽

Egfr Mutant ◽

Nsclc Patients ◽

Egfr Tkis

Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis. Methods. Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed. Results. A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS ( HR = 1.35 , 95% CI: 1.10-1.64, P = 0.003 ) and a tendency toward an unfavorable OS ( HR = 1.22 , 95% CI: 0.99-1.50, P = 0.068 ). Patients with deletion polymorphism had lower ORR ( OR = 0.60 , 95% CI: 0.42-0.85, P = 0.004 ) and DCR ( OR = 0.59 , 95% CI: 0.38-0.90, P = 0.014 ) compared with those without deletion. Conclusion. BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.

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Whole Brain Radiotherapy With and Without Concurrent Erlotinib in NSCLC with Brain Metastases: a multicentre, open-label, randomized, controlled phase 3 Trial

Neuro-Oncology ◽

10.1093/neuonc/noaa281 ◽

2020 ◽

Author(s):

Zhenzhou Yang ◽

Yan Zhang ◽

Rongqing Li ◽

Abulimiti Yisikandaer ◽

Biyong Ren ◽

...

Keyword(s):

Brain Metastases ◽

Objective Response ◽

Whole Brain Radiotherapy ◽

Combination Group ◽

Open Label ◽

Phase 3 ◽

Whole Brain ◽

Brain Radiotherapy ◽

Egfr Mutant ◽

Nsclc Patients

Abstract Background Erlotinib combined with whole brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase 2 single-arm trial of non-small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase 3, randomized trial. Methods NSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n=115) or WBRT combined with erlotinib arms (n=109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by Mini–Mental State Examination (MMSE). Results A total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months versus 9.2 months for WBRT-alone (p=0.601). Median PFS and overall survival (OS) of combination group were 5.3 versus 4.0 months (p=0.825) and 12.9 versus 10.0 months (p=0.545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 versus 12.8 months; p=0.164), PFS (8.8 versus 6.4 months; p=0.702) and OS (17.5 versus 16.9 months; p=0.221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no signiﬁcant differences in patients experiencing MMSE score change between the treatments. Conclusion Concurrent erlotinib with WBRT didn’t improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases.

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Clinical evaluation of recombinant interferon alfa-2a (Roferon-A) in metastatic melanoma using two different schedules .

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.8.1240 ◽

1987 ◽

Vol 5 (8) ◽

pp. 1240-1246 ◽

Cited By ~ 50

Author(s):

S S Legha ◽

N E Papadopoulos ◽

C Plager ◽

S Ring ◽

S P Chawla ◽

...

Keyword(s):

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Interferon Alfa ◽

Fixed Dose ◽

Ecog Performance Status ◽

Recombinant Interferon ◽

Level Of Activity ◽

Daily Schedule ◽

Major Toxicity

Based on the reports of activity of interferons against metastatic melanomas, we conducted a phase II study of recombinant interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ) in 66 patients with disseminated melanoma. All patients had excellent Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1), and no evidence of brain metastases. Thirty patients had previously received chemotherapy and the remainder were untreated. The first 35 patients were treated on a daily schedule starting with a Roferon-A dose of 3 X 10(6) U/d and escalating to a maximum of 36 X 10(6) U/d over a period of 12 days. Because of excessive toxicity, the second group of 31 patients were treated on a fixed dose of 18 X 10(6) U/d [corrected] three times weekly (TIW). Among the 62 evaluable patients, five achieved an objective response for a response rate of 8% (95% confidence limits, 3% to 18%). Four patients had minor regressions and eight patients had stability of disease. The responses were evenly distributed between the two dose schedules. The major toxicity of interferon consisted of a constitutional syndrome of anorexia, fever, weight loss, and fatigue, which required a dose reduction in 75% of the patients on the daily schedule. Our data revealed a modest level of activity, which was not influenced by prior treatment or by the dose or schedule of interferon. Because of substantial toxicity with the daily schedule, we recommend a dose of 18 X 10(6) U/d [corrected] if interferon is used in the treatment of patients with melanoma.

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Real-World Experience of Pembrolizumab Monotherapy in Patients with Recurrent or Persistent Cervical Cancer: A Korean Multi-Center Retrospective Study (KGOG1041)

Cancers ◽

10.3390/cancers12113188 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3188 ◽

Cited By ~ 1

Author(s):

Min Chul Choi ◽

Yong-Man Kim ◽

Jeong-Won Lee ◽

Yong Jae Lee ◽

Dong Hoon Suh ◽

...

Keyword(s):

Cervical Cancer ◽

Retrospective Study ◽

Antitumor Activity ◽

Real World ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Safety Data ◽

Ecog Performance Status ◽

Recurrent Cervical Cancer

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28–79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2. Forty-nine (41.9%) patients were stage ≥III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1–6). During the median follow-up of 4.9 months (range, 0.2–35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3–13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG ≤1) (n = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3–10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade ≥3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.

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An observational study of patients with advanced melanoma receiving pembrolizumab in a real-world U.S. community oncology practice.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e21015 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e21015-e21015

Author(s):

Charles Lance Cowey ◽

Frank Xiaoqing Liu ◽

Jenny Black-Shinn ◽

Kendall Lee Stevinson ◽

Marley Boyd ◽

...

Keyword(s):

Clinical Trials ◽

Brain Metastases ◽

Real World ◽

Performance Status ◽

Progression Free Survival ◽

Advanced Melanoma ◽

Ecog Performance Status ◽

Study Results ◽

Line Of Therapy ◽

Oncology Practice

e21015 Background: PD-1 monoclonal antibodies are promising immunotherapies approved for treatment of patients (pts) with advanced melanoma. As the first US FDA approved PD-1 antibody, pembrolizumab (pembro) has demonstrated efficacy and safety in clinical trial settings. However, patterns of real world utilization and pt outcomes associated with pembro are limited. Methods: Adult pts with advanced melanoma who initiated pembro between 9/1/ 2014-3/31/2016 were identified retrospectively fromelectronic health records (EHR) of McKesson Specialty Health and followed through 9/ 30/2016. Pts in clinical trials were excluded. Demographic, disease, treatment characteristics and reasons for treatment discontinuation of pembro were abstracted from structured data elements of the EHR with further supplementation of unstructured data within the patient chart (progress notes, radiology scan reports). Overall survival (OS) and physician-reported progression free survival (PFS) from pembro initiation were analyzed using Kaplan Meier analysis. Results: 182 pts, with a median follow-up of 9.9 mos (range = 0.0-25.0), were included. Median age at pembro initiation was 66.0 yrs; 30.8% had an elevated lactate dehydrogenase (LDH); 23.6% had brain metastases and 65.4% had an ECOG performance status of 0 or 1. The most common reason for pembro discontinuation was progression (45.5%) followed by treatment-related toxicity (24.4%). In the overall population, median PFS from pembro initiation was 4.2 mos (95% CI = 3.2-5.3). Median OS was 19.4 mos (14.0-NR) with 12 and 24-month survival probabilities of 61.4% (95% CI = 53.4-68.5) and 43.9% (95% CI = 31.1-55.9). In multivariable analyses, characteristics predictive of worse survival included receipt of pembro at a later line of therapy (HR = 3.36, p = 0.0013 for 3L+), presence of brain metastases (HR = 2.67, p = 0.0007) and elevated LDH (HR = 4.10, p < 0.0001). Conclusions: The study results are consistent with those from pembro clinical trials (KeyNote001) and are in support of the effectiveness of pembro in real world treatment of advanced melanoma. Presence of brain metastases, elevated LDH, and use of pembro 3L+ were associated with worse survival outcome.

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Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/DNA mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Clinical update.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3521 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3521-3521 ◽

Cited By ~ 8

Author(s):

Heinz-Josef Lenz ◽

Sara Lonardi ◽

Vittorina Zagonel ◽

Eric Van Cutsem ◽

M. Luisa Limon ◽

...

Keyword(s):

Clinical Benefit ◽

Low Dose ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Safety Data ◽

Ecog Performance Status ◽

Dna Mismatch ◽

Grade 3

3521 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI provided robust and durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up data will be presented. Methods: Patients with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg every 2 weeks + low-dose IPI 1 mg/kg every 6 weeks until disease progression or discontinuation. The primary endpoint was investigator-assessed objective response rate (ORR). Results: For all 45 patients (median follow-up was 13.8 months), ORR was 60% (95% CI 44.3–74.3). Responses were consistent with the overall population across subgroups including age, Eastern Cooperative Oncology Group (ECOG) performance status, prior adjuvant/neoadjuvant therapy, and mutation status (Table). Seven patients (16%) had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had any grade TRAEs leading to discontinuation. Updated response, survival, and safety data after a longer follow-up (median 19.9 months) will be presented. Conclusions: NIVO + low-dose IPI demonstrated robust and durable clinical benefit and was well tolerated. Evaluated subgroups had responses consistent with the overall population. NIVO + low-dose IPI may represent a new 1L treatment option for patients with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]

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Phase I/II trial of dose-reduced capecitabine in elderly patients with advanced colorectal cancer

Current Oncology ◽

10.3747/co.24.3516 ◽

2017 ◽

Vol 24 (4) ◽

pp. 261 ◽

Cited By ~ 4

Author(s):

M.D. Vincent ◽

D. Breader ◽

M.C. Cripps ◽

D.J. Jonker ◽

P. Klimo ◽

...

Keyword(s):

Colorectal Cancer ◽

Phase I ◽

Advanced Colorectal Cancer ◽

Response Rate ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Survival Duration ◽

Ecog Performance Status ◽

Pelvic Radiation

BackgroundCombination chemotherapy is associated with improved outcomes in trials of selected fit patients with advanced colorectal cancer (acrc). For older or less-fit patients, combination chemotherapy is associated with greater toxicity and less benefit. Capecitabine monotherapy is a reasonable option for those patients, but the optimal dose remains controversial.MethodsA multicentre phase i/ii trial of reduced-dose capecitabine (2000 mg/m2, days 1–14 every 21 days) was conducted in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ecog) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (ldh) (n = 105), or prior pelvic radiation (n = 54). Based on phase i results, patients with prior pelvic radiation received capecitabine 750 mg/m2 twice daily. The goal was to ascertain efficacy in a design that was unlikely to cause high levels of toxicity.Results Median age in the patient cohort was 72 years. A median of 5 and a mean of 8 capecitabine cycles were given (range: 0–50 cycles). Grade 3 or 4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand–foot syndrome, 7.7% diarrhea). The response rate was 13.6%, with a 69.7% disease control rate. Median progression-free survival (pfs) was 5.6 months. Post progression, 56 patients received further capecitabine monotherapy (median of 4 additional cycles). Median overall survival duration for the patients was 14.3 months. Median survival was significantly higher for those who, at baseline, had an ecog performance status of 0 (compared with 1 or more) and normal ldh (compared with elevated ldh).Conclusions Toxicity is less with dose-reduced capecitabine than with historical full-dose capecitabine, with only a small trade-off in efficacy, seen as a lower objective response rate. The improved tolerability could lead to an increased number of cycles of therapy, and pfs appears to be consistently higher at the lower dose. Those observations should, in the absence of a head-to-head clinical trial, be viewed as compelling evidence that 1000 mg/m2, or even 750 mg/m2, twice daily is an appropriate dose in elderly or frail patients with acrc.

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FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide–platinum combination in patients with neuroendocrine carcinomas grade 3

Endocrine Related Cancer ◽

10.1530/erc-12-0002 ◽

2012 ◽

Vol 19 (6) ◽

pp. 751-757 ◽

Cited By ~ 62

Author(s):

O Hentic ◽

P Hammel ◽

A Couvelard ◽

V Rebours ◽

M Zappa ◽

...

Keyword(s):

Serum Alkaline Phosphatase ◽

Performance Status ◽

Objective Response ◽

Good Condition ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Second Line ◽

Ecog Performance Status ◽

Grade 3 ◽

Neuroendocrine Carcinomas

Patients with neuroendocrine carcinomas (NECs) grade 3 have a poor prognosis. Etoposide–platinum combination is the standard chemotherapy but the role of a second-line therapy remains unknown. Irinotecan alone or in combination has shown some efficacy in patients treated for small cell lung cancer which had pathological similarities with neuroendocine tumors. The aim of this study is to determine safety and efficacy of the FOLFIRI regimen in patients with NECs grade 3 after failure of etoposide–platinum combination. This study was retrospective, including patients with NECs grade 3 and treated with the FOLFIRI regimen after progression or toxicity of etoposide–platinum combination in first-line. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≥3 and/or serum alkaline phosphatase ≥5×upper limit of normal value (ULN) and/or bilirubin ≥1.5×ULN were excluded. Among 39 patients who failed etoposide–platinum combination, 19 (49%; 12 women, median age 53 (29–78) years) received the FOLFIRI regimen with a median number of 6 (1–16) courses. Six patients (31%) had at least one episode of grades 3–4 toxicity (neutropenia, n=3; diarrhea, n=3) without toxic death. Six patients (31%) had objective response, 6 (31%) stable disease, and 7 (38%) tumor progression. Median progression-free survival under FOLFIRI was 4 months. Overall survival was 18 vs 6.8 months in noneligible patients. FOLFIRI regimen is a safe and potentially efficient chemotherapy given as second-line in patients with NECs grade 3 who remain in good condition and with correct liver tests after failure of etoposide–platinum combination. These results should be confirmed in a future prospective study.

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Phase II Multicenter Study of Abiraterone Acetate Plus Prednisone Therapy in Patients With Docetaxel-Treated Castration-Resistant Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.9259 ◽

2010 ◽

Vol 28 (9) ◽

pp. 1496-1501 ◽

Cited By ~ 316

Author(s):

Daniel C. Danila ◽

Michael J. Morris ◽

Johann S. de Bono ◽

Charles J. Ryan ◽

Samuel R. Denmeade ◽

...

Keyword(s):

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Specific Antigen ◽

Circulating Tumor Cell ◽

Abiraterone Acetate ◽

Phase Iii ◽

Castration Resistant Prostate Cancer ◽

Ecog Performance Status ◽

Castration Resistant

Purpose Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate tissue. This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy. Patients and Methods Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA (1,000 mg daily) with prednisone (5 mg twice daily). Twenty-seven (47%) patients had received prior ketoconazole. The primary outcome was ≥ 50% prostate-specific antigen (PSA) decline, with objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and changes in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and circulating tumor cell (CTC) numbers. Safety was also evaluated. Results A ≥ 50% decline in PSA was confirmed in 22 (36%) patients, including 14 (45%) of 31 ketoconazole-naïve and seven (26%) of 27 ketoconazole-pretreated patients. Partial responses were seen in four (18%) of 22 patients with RECIST-evaluable target lesions. Improved ECOG PS was seen in 28% of patients. Median time to PSA progression was 169 days (95% CI, 82 to 200 days). CTC conversions with treatment from ≥ 5 to < 5 were noted in 10 (34%) of 29 patients. The majority of AA-related adverse events were grade 1 to 2, and no AA-related grade 4 events were seen. Conclusion AA plus prednisone was well tolerated, with encouraging antitumor activity in heavily pretreated CRPC patients. The incidence of mineralocorticoid-related toxicities (hypertension or hypokalemia) was reduced by adding low-dose prednisone. The combination of AA plus prednisone is recommended for phase III investigations.

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A multicentre analysis of abiraterone acetate in Canadian patients with metastatic castration resistant prostate cancer

Canadian Urological Association Journal ◽

10.5489/cuaj.1891 ◽

2014 ◽

Vol 8 (9-10) ◽

pp. 583 ◽

Cited By ~ 7

Author(s):

Ravinder Clayton ◽

Jackson Wu ◽

Daniel Y Heng ◽

Scott A North ◽

Urban Emmenegger ◽

...

Keyword(s):

Prostate Cancer ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Specific Antigen ◽

Abiraterone Acetate ◽

Castration Resistant Prostate Cancer ◽

Ecog Performance Status ◽

Castration Resistant ◽

Study Results

Introducton: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone.Methods: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted.Results: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events.Conclusions: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.

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