More highlights in Breast Cancer

Recent breast cancer studies reveal significant advancements: ovarian suppression plus endocrine therapy boosts survival in pre-menopausal HER2+ patients; ribociclib shows greater benefit and fewer adverse events in younger HR+/HER2- patients; pembrolizumab enhances survival in early-stage TNBC; and nodal radiotherapy may now be effectively shortened to 3 weeks.

Pre-menopausal patients with HER2+ early breast cancer benefit from ovarian function suppression plus endocrine therapy

Previously, the phase 3 HERA trial (NCT00045032) showed that 1 year of adjuvant trastuzumab after chemotherapy for patients with HER2-positive early breast cancer significantly improved long-term disease-free survival (DFS), compared with observation [1].

Based on a subgroup analysis of pre-menopausal patients in HERA (n=965), Dr Sung Gwe Ahn (Yonsei University Hospital, South Korea) showed that adding ovarian function suppression to endocrine therapy improved long-term survival outcomes in this subgroup [2]. The 10-year DFS increased from 59.6% to 70.9% (HR 0.68; 95% CI 0.53–0.88) and the 10-year overall survival (OS) increased from 74.0% to 84.7% (HR 0.64; 95% CI 0.46–0.89). In addition, in patients receiving ovarian function suppression, endocrine therapy with an aromatase inhibitor was superior to tamoxifen. The 10-year DFS was 78.7% versus 65.2% (HR 0.54; 95% CI 0.38–0.75) and the 10-year OS was 91.3% versus 79.7% (HR 0.48; 95% CI 0.30–0.77), respectively.

More benefit and fewer adverse events with ribociclib in younger patients

The phase 3 NATALEE trial showed a statistically significant invasive DFS (iDFS) benefit of ribociclib plus a non-steroidal aromatase inhibitor (NSAI) versus NSAI alone (HR 0.75; 95% CI 0.63–0.89; P=0.0006) in patients with HR+/HER2- early breast cancer [3]. Updated study data was presented by Prof. Peter Fasching (University Hospital Erlangen, Germany) [4].

After a median follow-up of 44.2 months, iDFS was still significantly improved in the ribociclib plus NSAI arm compared with NSAI alone (HR 0.72; 95% CI 0.61–0.84; P<0.0001). The iDFS benefit was observed across subgroups, stratified by either nodal status or disease stage. Safety data was consistent with the previous analysis.

In a post-hoc analysis of NATALEE, Dr Sherene Loi (Peter MacCallum Cancer Centre, Australia) presented that younger patients (<40 years; n=543), a group that traditionally shows worse treatment outcomes, benefitted more from ribociclib plus NSAI over NSAI alone than older patients (≥40 years; n=4,558) [5]. The absolute 3-year iDFS benefit was 5.1% versus 2.8%, the absolute 3-year distant DFS benefit was 5.1% versus 2.4%, and the absolute OS benefit was 1.9 years versus 0.9 years. In addition, younger patients had fewer serious adverse events and fewer discontinuations.

Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab improves OS in early-stage TNBC

Previous results of the phase 3 KEYNOTE-522 trial showed a significantly improved pathologic complete response (pCR) rate and event-free survival after neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab, compared with neoadjuvant chemotherapy alone in patients with high-risk, early-stage triple-negative breast cancer (TNBC) [6,7].

Prof. Peter Schmid (Barts Cancer Institute, UK) now presented OS results after 75.1 months of follow-up [8]. The 5-year OS rate was 86.6% in participants treated with pembrolizumab (n=784) versus 81.7% in participants treated with placebo (HR 0.66; 95% CI 0.50–0.87; P=0.0015).

The absolute OS benefit of pembrolizumab was more pronounced in participants without a pCR (71.8% vs 65.7%), compared with those with a pCR (95.1% vs 94.4%). With longer follow-up, no new safety concerns were identified.

Nodal radiotherapy for breast cancer no longer needs 5 weeks

Currently, hypofractionated radiotherapy is the standard regimen for whole breast radiotherapy. However, normofractionated radiotherapy is still standard in most countries for loco-regional early breast cancer.

The phase 3 HypoG-01 UNICANCER trial (NCT03127995) assessed the non-inferiority of hypofractionated radiotherapy (40 Gy in 15 fractions; 3 weeks) versus normofractionated radiotherapy (50 Gy in 25 fractions; 5 weeks). The 1,265 participants, operated for T1-3, N0-3, M0 breast cancer with an indication for regional nodes radiotherapy, were 1:1 randomised to either treatment arm. Dr Sofia Rivera (Institut Gustave Roussy, France) presented the results [9].

After a median follow-up of 4.8 years, non-inferiority was observed in cumulative ipsilateral arm lymphedema rate, the primary endpoint of the study: 33.3% in the hypofractionated arm versus 32.8% in the normofractionated arm (HR 1.02; 95% CI 0.83–1.26; P_{non-inferiority} <0.001). Also, no sign of a detrimental effect of hypofractionated radiotherapy was observed on OS, breast cancer-specific survival, local recurrence-free survival, distant DFS, and cumulative range of shoulder motion impairment rate (secondary endpoints). Based on these results, Dr Rivera concluded that “the new standard for nodal radiation is 3 weeks.”

1. Cameron D, et al. Lancet. 2017;389:1195-1205.
2. Ahn SG, et al. Ovarian function suppression in HR-positive, HER2-positive breast cancer: An exploratory analysis from the HERA trial. Abstract 233MO, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
3. Slamon D, et al. N Eng J Med 2024;390:1080-1091.
4. Fasching PA, et al. Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (Pts) with HR+/HER2− early breast cancer (EBC): 4-year outcomes from the NATALEE trial. Abstract LBA13, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
5. Loi S, et al. Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in younger patients (pts) with HR+/HER2− early breast cancer (EBC) in NATALEE. Abstract 235MO, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
6. Schmid P, et al. N Engl J Med 2020;382:810-821.
7. Schmid P, et al. N Engl J Med 2022;386:556-667.
8. Schmid P, et al. Neoadjuvant pembrolizumab or placebo + chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage triple-negative breast cancer: overall survival results from the phase 3 KEYNOTE-522 study. Abstract LBA4, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
9. Rivera S, et al. Locoregional hypo vs normofractionated RT in early breast cancer: 5 years results of the HypoG-01 phase III UNICANCER trial. Abstract 231O, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024