Conflicting Hypofractionated Radiotherapy Prostate Cancer Trial Results Revealed

Results from two trials shed light on use of hypofractionated radiotherapy in prostate cancer

medwireNews: Opposing conclusions from the HYPRO and CHHiP trials of hypofractionated radiotherapy for prostate cancer have been published in The Lancet Oncology.

The phase III open-label HYPRO study investigators report that hypofractionated radiotherapy (19 fractions of 3.4 Gy, delivered three times a week) was not superior to conventional radiation (78.0 Gy in 39 fractions of 2.0 Gy, five times a week) for patients with intermediate- or high-risk localised prostate cancer.

Five-year relapse-free survival was 80.5% for the 407 patients assigned to receive hypofractionated radiotherapy versus 77.1% of those given conventional treatment, with an adjusted hazard ratio of 0.86, say Luca Incrocci, from Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and co-authors.

“Hypofractionated treatment with 19 fractions of 3.4 Gy cannot be regarded as the standard of care for patients with intermediate-risk and high-risk prostate cancer”, they write, but add that hypofractionated therapy could be considered for select patients with gastrointestinal or urinary issues at baseline.

By contrast, the authors of the phase III CHHiP trial conclude that their high-dose intensity-modulated radiotherapy hypofractionated regimen is non-inferior to conventional radiotherapy and can therefore be “recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer”.

Five-year biochemical or clinical failure-free survival was 88.3% for the 1065 patients who received 74 Gy delivered in 37 fractions over 7.4 weeks versus 90.6% and 85.9% for the patients who were allocated a 60 Gy and 57 Gy hypofractionated regimen given in 20 fractions over 4 weeks and 19 fractions over 3.8 weeks, respectively.

Thus, the 60 Gy hypofractionated, but not the 57 Gy hypofractionated, regimen was non-inferior to conventional radiotherapy with a HR of 0.84, say David Dearnaley, from The Institute of Cancer Research in London, UK, and CHHiP co-investigators.

William Robert Lee, from Duke University School of Medicine in Durham, North Carolina, USA, explains in an accompanying comment, that the “apparent discordance” in the HYPRO and CHHiP authors’ recommendations may be explained by the different superiority and non-inferiority trial designs.

He supports the HYPRO investigators’ conclusion that their hypofractionation regimen should not be adopted but agrees that the CHHiP results suggest that “hypofractionation will not result in any loss of efficacy and could make treatment less expensive and more convenient for patients when compared with conventionally fractionated radiotherapy.”

William Robert Lee concludes that upcoming results from the non-inferiority PROFIT trial testing the same hypofractionated regimen used in CHHiP will add to evidence on the use of a 4-week schedule.

“For practitioners interested in judicious use of resources and patients' convenience, this regimen can be presented confidently and discussed with patients as an alternative to conventional fractionation”, he says.

References

Incrocci L, Wortel RC, Alemayehu WG, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 2016; Advance online publication 20 June. doi:10.1016/S1470-2045(16)30070-5

Dearnaley D, Syndikus I, Mossop H, 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; Advance online publication 20 June. doi:10.1016/S1470-2045(16)30102-4

Lee WR. Hypofractionation for prostate cancer: tested and proven. Lancet Oncol 2016; Advance online publication 20 June. doi:10.1016/S1470-2045(16)30150-4

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