A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†

I. A. McNeish; J. A. Ledermann; L. Webber; L. James; S. B. Kaye; M. Hall; G. Hall; A. Clamp; H. Earl; S. Banerjee; R. Kristeleit; F. Raja; A. Feeney; C. Lawrence; L. Dawson-Athey; M. Persic; I. Khan

doi:10.1093/annonc/mdu363

A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†

I. A. McNeish, J. A. Ledermann, L. Webber, L. James, S. B. Kaye, M. Hall, G. Hall, A. Clamp, H. Earl, S. Banerjee, R. Kristeleit, F. Raja, A. Feeney, C. Lawrence, L. Dawson-Athey, M. Persic, I. Khan

Population & Patient Health

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Abstract

BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer.

PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/week ×6 with 2-week break) plus saracatinib (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 versus ≥6 months/no prior taxane). The primary end point was progression-free survival (PFS) rate at 6 months. Secondary end points included overall survival (OS) and response rate (RR).

RESULTS: A total of 107 patients, median age 63 years, were randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6-month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54; P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo), abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 5.7%). Febrile neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%). Response, PFS and OS were all significantly (P < 0.05) better in patients with taxane interval ≥6 months/no prior taxane (n = 85) than those <6 months (n = 22), regardless of randomisation.

CONCLUSIONS: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups.

TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062.

Original language	English
Pages (from-to)	1988-1995
Number of pages	8
Journal	Annals of oncology : official journal of the European Society for Medical Oncology / ESMO
Volume	25
Issue number	10
DOIs	https://doi.org/10.1093/annonc/mdu363
Publication status	Published - 1 Oct 2014

Keywords

ovarian cancer
platinum-resistant
Src
taxane-free-interval
weekly paclitaxel

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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McNeish, I. A., Ledermann, J. A., Webber, L., James, L., Kaye, S. B., Hall, M., Hall, G., Clamp, A., Earl, H., Banerjee, S., Kristeleit, R., Raja, F., Feeney, A., Lawrence, C., Dawson-Athey, L., Persic, M., & Khan, I. (2014). A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 25(10), 1988-1995. https://doi.org/10.1093/annonc/mdu363

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title = "A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†",

abstract = "BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer.PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/week ×6 with 2-week break) plus saracatinib (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 versus ≥6 months/no prior taxane). The primary end point was progression-free survival (PFS) rate at 6 months. Secondary end points included overall survival (OS) and response rate (RR).RESULTS: A total of 107 patients, median age 63 years, were randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6-month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54; P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo), abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 5.7%). Febrile neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%). Response, PFS and OS were all significantly (P < 0.05) better in patients with taxane interval ≥6 months/no prior taxane (n = 85) than those <6 months (n = 22), regardless of randomisation.CONCLUSIONS: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups.TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062.",

keywords = "ovarian cancer, platinum-resistant, Src, taxane-free-interval, weekly paclitaxel",

author = "McNeish, {I. A.} and Ledermann, {J. A.} and L. Webber and L. James and Kaye, {S. B.} and M. Hall and G. Hall and A. Clamp and H. Earl and S. Banerjee and R. Kristeleit and F. Raja and A. Feeney and C. Lawrence and L. Dawson-Athey and M. Persic and I. Khan",

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McNeish, IA, Ledermann, JA, Webber, L, James, L, Kaye, SB, Hall, M, Hall, G, Clamp, A, Earl, H, Banerjee, S, Kristeleit, R, Raja, F, Feeney, A, Lawrence, C, Dawson-Athey, L, Persic, M & Khan, I 2014, 'A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†', Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, vol. 25, no. 10, pp. 1988-1995. https://doi.org/10.1093/annonc/mdu363

A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†. / McNeish, I. A.; Ledermann, J. A.; Webber, L. et al.
In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, Vol. 25, No. 10, 01.10.2014, p. 1988-1995.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†

AU - McNeish, I. A.

AU - Ledermann, J. A.

AU - Webber, L.

AU - James, L.

AU - Kaye, S. B.

AU - Hall, M.

AU - Hall, G.

AU - Clamp, A.

AU - Earl, H.

AU - Banerjee, S.

AU - Kristeleit, R.

AU - Raja, F.

AU - Feeney, A.

AU - Lawrence, C.

AU - Dawson-Athey, L.

AU - Persic, M.

AU - Khan, I.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer.PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/week ×6 with 2-week break) plus saracatinib (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 versus ≥6 months/no prior taxane). The primary end point was progression-free survival (PFS) rate at 6 months. Secondary end points included overall survival (OS) and response rate (RR).RESULTS: A total of 107 patients, median age 63 years, were randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6-month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54; P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo), abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 5.7%). Febrile neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%). Response, PFS and OS were all significantly (P < 0.05) better in patients with taxane interval ≥6 months/no prior taxane (n = 85) than those <6 months (n = 22), regardless of randomisation.CONCLUSIONS: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups.TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062.

AB - BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer.PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/week ×6 with 2-week break) plus saracatinib (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 versus ≥6 months/no prior taxane). The primary end point was progression-free survival (PFS) rate at 6 months. Secondary end points included overall survival (OS) and response rate (RR).RESULTS: A total of 107 patients, median age 63 years, were randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6-month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54; P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo), abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 5.7%). Febrile neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%). Response, PFS and OS were all significantly (P < 0.05) better in patients with taxane interval ≥6 months/no prior taxane (n = 85) than those <6 months (n = 22), regardless of randomisation.CONCLUSIONS: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups.TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062.

KW - ovarian cancer

KW - platinum-resistant

KW - Src

KW - taxane-free-interval

KW - weekly paclitaxel

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U2 - 10.1093/annonc/mdu363

DO - 10.1093/annonc/mdu363

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C2 - 25070546

AN - SCOPUS:84964313307

SN - 0923-7534

VL - 25

SP - 1988

EP - 1995

JO - Annals of oncology : official journal of the European Society for Medical Oncology / ESMO

JF - Annals of oncology : official journal of the European Society for Medical Oncology / ESMO

IS - 10

ER -

McNeish IA, Ledermann JA, Webber L, James L, Kaye SB, Hall M et al. A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2014 Oct 1;25(10):1988-1995. doi: 10.1093/annonc/mdu363

A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†

Abstract

Keywords

UN SDGs

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