Research Insights - 1
Timing of CDK 4/6 inhibition in hormone receptor-positive, HER2-negative advanced
breast cancer (SONIA trial, phase III)
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Addition of CDK 4/6 inhibitor (CDK 4/6i) to aromatase inhibitor benefits hormone
receptor-positive, HER2-negative advanced breast cancer in first-line treatment.
Uncertain if delaying CDK 4/6i to second-line treatment is equally effective.
Most international guidelines advise first-line use, despite prolonged toxicity and a
steep increase in costs compared to use in second-line. No head to head comparison
available.
SONIA trial: 1050 women, randomized to first-line nonsteroidal aromatase inhibitor
(NSAI) + CDK 4/6i followed by fulvestrant upon disease progression, or first-line
NSAI followed by fulvestrant + CDK 4/6i upon disease progression.
Median follow-up 37 months: 46 months median survival with first-line CDK 4/6i, 54
months with second-line CDK 4/6i.
First-line use of CDK4/6i + ET does not provide statistically significant, nor clinically
meaningful PFS benefit compared to second-line use in women with HR+, HER2ABC.
First-line CDK 4/6i group stayed on treatment for 25 months; second-line group for
8.1 months, which was associated with 42 percent more grade ≥3 toxicities.
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Authors recommend use of CDK 4/6i as second line of treatment as the use in firstline prolongs the time on CDK4/6i by 16.4 months and increases toxicity and costs.
Second-line use may thus be a preferred option for the majority of patients.
Source: Meeting Abstract | 2023 ASCO Annual Meeting II
https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.17_suppl.LBA1000
Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer
(IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised
controlled trial
● A tumour-bed boost delivered after whole-breast radiotherapy increases local cancercontrol rates but requires more patient visits and can increase breast hardness.
● IMPORT HIGH study tested simultaneous integrated boost against sequential boost
with the aim of reducing treatment duration
● A phase 3, open-label, randomized controlled trial with 2600 patients into 3 groups of
1:1:1 ratio
○ Control group: 40 Gy in 15 fractions to the whole breast and 16 Gy in 8
fractions sequential photon tumour-bed boost.
○ Test group 1: 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions
to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to
the tumour-bed volume.
○ Test group 2: 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions
to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to
the tumour-bed volume.
● Primary endpoint was ipsilateral breast tumour relapse (IBTR)
● Authors concluded that In all groups 5-year IBTR incidence was lower than the 5%
originally expected regardless of boost sequencing. Dose-escalation is not
advantageous. 5-year moderate or marked adverse event rates were low using small
boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and
reduced patient visits.
Source: The Lancet, VOLUME 401, ISSUE 10394, P2124-2137, JUNE 24, 2023
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00619-0/fulltext