CHHiP: trial | Bending the Curve: Trial by Trial

CHHiP

Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer: CHHIP

Population

Men with localised prostate cancer (pT1b-T3aN0M0)

Design

Randomised (1:1:1), non-inferiority, phase 3 trial, 71 centres, October 2002 to June 2011: 3216 men with localised prostate cancer (pT1b-T3aN0M0) assigned to 74 Gy in 37 fractions over 7.4 weeks, 60 Gy in 20 fractions over 4 weeks, or 57 Gy in 19 fractions over 3.8 weeks, all with intensity-modulated techniques. Most patients had 3 to 6 months of neoadjuvant and concurrent androgen suppression. Primary endpoint: time to biochemical or clinical failure; critical hazard ratio for non-inferiority 1.208. Analysis by intention to treat (5-year outcomes, pre-planned).

Primary endpoint

BCF-free survival

Arms

74 Gy in 37 fractions (control, n = 1,065): 74 Gy in 37 fractions over 7.4 weeks, intensity-modulated radiotherapy
60 Gy in 20 fractions (experimental, n = 1,074): 60 Gy in 20 fractions over 4 weeks, intensity-modulated radiotherapy
57 Gy in 19 fractions (experimental, n = 1,077): 57 Gy in 19 fractions over 3.8 weeks, intensity-modulated radiotherapy

People

Dearnaley D, CHHiP Investigators

BCF-free survivalHR 0.84Δ 60-month BCF-free survival+2.3 pointsBCF-free survivalHR 1.2Δ 60-month BCF-free survival−2.4 pointsΔ 60-month RTOG grade 2 or worse gastrointestinal toxicity−1.8 pointsΔ 60-month RTOG grade 2 or worse genitourinary toxicity+2.6 points

Show the numbers

Results reported for CHHiP
Endpoint	Analysis	60 Gy in 20 fractions / 57 Gy in 19 fractions	74 Gy in 37 fractions	Effect
BCF-free survivalProportion free of biochemical or clinical failure at 5 years (primary endpoint: time to biochemical or clinical failure)	primarymedian follow-up 62.4 monthsDearnaley 2016	90.6% at 5 y (88.5–92.3%)	88.3% at 5 y (86.0–90.2%)	HR 0.84P=0.0018Hazard ratio 0.84 has a 90% CI of 0.68 to 1.03; the P value is for non-inferiority (critical HR 1.208). 60 Gy was non-inferior to 74 Gy.
BCF-free survivalProportion free of biochemical or clinical failure at 5 years (primary endpoint: time to biochemical or clinical failure)	primarymedian follow-up 62.4 monthsDearnaley 2016	85.9% at 5 y (83.4–88.0%)	88.3% at 5 y (86.0–90.2%)	HR 1.2P=0.48Hazard ratio 1.20 has a 90% CI of 0.99 to 1.46; the P value is for non-inferiority (critical HR 1.208). Non-inferiority could not be claimed for 57 Gy.
RTOG grade 2 or worse gastrointestinal toxicityEstimated cumulative 5-year incidence of RTOG grade 2 or worse bowel adverse events	primaryDearnaley 2016	11.9% at 5 y	13.7% at 5 y	Clinician-reported (RTOG). 111, 105 and 95 events. The abstract reports no significant differences in side-effects at 5 years.
RTOG grade 2 or worse genitourinary toxicityEstimated cumulative 5-year incidence of RTOG grade 2 or worse bladder adverse events	primaryDearnaley 2016	11.7% at 5 y	9.1% at 5 y	Clinician-reported (RTOG). 66, 88 and 57 events. The abstract reports no significant differences in side-effects at 5 years.

Results reported for CHHiP
Endpoint	Analysis	60 Gy in 20 fractions / 57 Gy in 19 fractions	74 Gy in 37 fractions	Effect
BCF-free survivalProportion free of biochemical or clinical failure at 5 years (primary endpoint: time to biochemical or clinical failure)	primarymedian follow-up 62.4 monthsDearnaley 2016	90.6% at 5 y (88.5–92.3%)	88.3% at 5 y (86.0–90.2%)	HR 0.84P=0.0018Hazard ratio 0.84 has a 90% CI of 0.68 to 1.03; the P value is for non-inferiority (critical HR 1.208). 60 Gy was non-inferior to 74 Gy.
BCF-free survivalProportion free of biochemical or clinical failure at 5 years (primary endpoint: time to biochemical or clinical failure)	primarymedian follow-up 62.4 monthsDearnaley 2016	85.9% at 5 y (83.4–88.0%)	88.3% at 5 y (86.0–90.2%)	HR 1.2P=0.48Hazard ratio 1.20 has a 90% CI of 0.99 to 1.46; the P value is for non-inferiority (critical HR 1.208). Non-inferiority could not be claimed for 57 Gy.
RTOG grade 2 or worse gastrointestinal toxicityEstimated cumulative 5-year incidence of RTOG grade 2 or worse bowel adverse events	primaryDearnaley 2016	11.9% at 5 y	13.7% at 5 y	Clinician-reported (RTOG). 111, 105 and 95 events. The abstract reports no significant differences in side-effects at 5 years.
RTOG grade 2 or worse genitourinary toxicityEstimated cumulative 5-year incidence of RTOG grade 2 or worse bladder adverse events	primaryDearnaley 2016	11.7% at 5 y	9.1% at 5 y	Clinician-reported (RTOG). 66, 88 and 57 events. The abstract reports no significant differences in side-effects at 5 years.

Appears in

2016 Shorter radiotherapy: hypofractionation and SBRT (CHHiP, PACE-B)

Sources

Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2016;17(8):1047-1060.
PubMed DOI