Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1118 - 1123 |
| Number of pages | 6 |
| Journal | Annals of Oncology |
| Volume | 26 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2015 |
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EVERSUN: a phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma. / Davis, Ian; Long, Anne; Yip, Sonia; Espinoza, David; Thompson, John F; Kichenadsasse, Ganessan; Harrison, Michelle; Lowenthal, Ray M; Pavlakis, Nick; Azad, Arun; Kannourakis, George; Steer, Christopher; Goldstein, David A; Shapiro, Jeremy; Harvie, Rozelle M; Jovanovic, Lidija; Hudson, Amanda L; Nelson, Colleen C; Stockler, Martin R; Martin, Axel V.
In: Annals of Oncology, Vol. 26, No. 6, 2015, p. 1118 - 1123.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - EVERSUN: a phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma
AU - Davis, Ian
AU - Long, Anne
AU - Yip, Sonia
AU - Espinoza, David
AU - Thompson, John F
AU - Kichenadsasse, Ganessan
AU - Harrison, Michelle
AU - Lowenthal, Ray M
AU - Pavlakis, Nick
AU - Azad, Arun
AU - Kannourakis, George
AU - Steer, Christopher
AU - Goldstein, David A
AU - Shapiro, Jeremy
AU - Harvie, Rozelle M
AU - Jovanovic, Lidija
AU - Hudson, Amanda L
AU - Nelson, Colleen C
AU - Stockler, Martin R
AU - Martin, Axel V
PY - 2015
Y1 - 2015
N2 - Background: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods: A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results: We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71 male, favourable risk 16 , intermediate risk 84 . Cycle 2 commenced within 14 weeks for 80 of participants; 64 received =22 weeks of alternating therapy; 78 received =22 weeks of any treatment. PFS6m was 29/55 (53 ; 95 confidence interval [CI] 40 to 66 ). Tumour response rate was 7/55 (13 ; 95 CI 4 to 22 , all partial responses). After median follow-up of 20 months, 47 of 55 (86 ) had progressed with a median progression-free survival of 8 months (95 CI 5-10), and 30 of 55 (55 ) had died with a median OS of 17 months (95 CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions: The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.
AB - Background: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods: A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results: We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71 male, favourable risk 16 , intermediate risk 84 . Cycle 2 commenced within 14 weeks for 80 of participants; 64 received =22 weeks of alternating therapy; 78 received =22 weeks of any treatment. PFS6m was 29/55 (53 ; 95 confidence interval [CI] 40 to 66 ). Tumour response rate was 7/55 (13 ; 95 CI 4 to 22 , all partial responses). After median follow-up of 20 months, 47 of 55 (86 ) had progressed with a median progression-free survival of 8 months (95 CI 5-10), and 30 of 55 (55 ) had died with a median OS of 17 months (95 CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions: The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.
UR - http://annonc.oxfordjournals.org/content/26/6/1118.full.pdf+html
U2 - 10.1093/annonc/mdv078
DO - 10.1093/annonc/mdv078
M3 - Article
VL - 26
SP - 1118
EP - 1123
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 6
ER -