Abstract
BACKGROUND: Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed. PATIENTS AND METHODS: Patients aged ≥18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017). RESULTS: KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months (95% CI, 20.2-30.4) and 38.6 months (95% CI, 27.2-not reached), respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months (95% CI, 5.8-11.1) and 16.9 months (95% CI, 9.3-35.5), respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE. CONCLUSIONS: This 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, NCT01295827.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 582-588 |
| Number of pages | 7 |
| Journal | Annals of oncology : official journal of the European Society for Medical Oncology |
| Volume | 30 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2019 |
| Externally published | Yes |
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Keywords
- long-term follow-up
- melanoma
- metastatic
- overall survival
- pembrolizumab
- treatment-naive
ASJC Scopus subject areas
- Hematology
- Oncology
Cite this
Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. / Hamid, O.; Robert, C.; Daud, A.; Hodi, F. S.; Hwu, W. J.; Kefford, R.; Wolchok, J. D.; Hersey, P.; Joseph, Richard W; Weber, J. S.; Dronca, Roxana S; Mitchell, T. C.; Patnaik, A.; Zarour, H. M.; Joshua, A. M.; Zhao, Q.; Jensen, E.; Ahsan, S.; Ibrahim, N.; Ribas, A.
In: Annals of oncology : official journal of the European Society for Medical Oncology, Vol. 30, No. 4, 01.04.2019, p. 582-588.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001
AU - Hamid, O.
AU - Robert, C.
AU - Daud, A.
AU - Hodi, F. S.
AU - Hwu, W. J.
AU - Kefford, R.
AU - Wolchok, J. D.
AU - Hersey, P.
AU - Joseph, Richard W
AU - Weber, J. S.
AU - Dronca, Roxana S
AU - Mitchell, T. C.
AU - Patnaik, A.
AU - Zarour, H. M.
AU - Joshua, A. M.
AU - Zhao, Q.
AU - Jensen, E.
AU - Ahsan, S.
AU - Ibrahim, N.
AU - Ribas, A.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - BACKGROUND: Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed. PATIENTS AND METHODS: Patients aged ≥18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017). RESULTS: KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months (95% CI, 20.2-30.4) and 38.6 months (95% CI, 27.2-not reached), respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months (95% CI, 5.8-11.1) and 16.9 months (95% CI, 9.3-35.5), respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE. CONCLUSIONS: This 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, NCT01295827.
AB - BACKGROUND: Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed. PATIENTS AND METHODS: Patients aged ≥18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017). RESULTS: KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months (95% CI, 20.2-30.4) and 38.6 months (95% CI, 27.2-not reached), respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months (95% CI, 5.8-11.1) and 16.9 months (95% CI, 9.3-35.5), respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE. CONCLUSIONS: This 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, NCT01295827.
KW - long-term follow-up
KW - melanoma
KW - metastatic
KW - overall survival
KW - pembrolizumab
KW - treatment-naive
UR - http://www.scopus.com/inward/record.url?scp=85065574127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065574127&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdz011
DO - 10.1093/annonc/mdz011
M3 - Article
C2 - 30715153
AN - SCOPUS:85065574127
VL - 30
SP - 582
EP - 588
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 4
ER -