Endocrine therapy alone versus targeted combination strategy as first line treatment in elderly patients with hormone receptor-positive advanced breast cancer: Meta-analysis of phase II and III randomized clinical trial

Endocrine therapy alone vs targeted combination strategy as first line

treatment in elderly patients with hormone receptor-positive advanced breast

cancer: meta-analysis of Phase II and III randomized clinical trials

• The rate of elderly Metastatic Breast Cancer (MBC) patients will increase in the next years due to the increasing longevity of the population and treatments improvement.

• The physician decision-making process should ensure the best treatment options taking in consideration age, concomitant diseases, life expectancy and quality of life.

• Establishing recommendations for management of older MBC patients is challenging because of very limited level 1 evidence in this population.

• Targeted and/or combined endocrine approaches have been investigated as first-line treatment in MBC patients.

• In elderly patients, due to the multi-morbidity and the major toxicity associated with the targeted agents, the combination strategy is widely discussed.

• A systematic literature search of the electronic database PubMed, EMBASE, Cochrane Library and Web of Science was conducted to identify phase II and phase III randomized controlled trials investigating the combination strategy compared to endocrine therapy (ET) alone for the first-line treatment of HR-positive/HER2-negative MBC.

• The present analysis has been conducted accordingly to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PROSPERO registration number CRD42019120215. Full protocol is freely available on the PROSPERO website.

• 8 studies were included in the meta-analysis including 2091 patients diagnosed with HR-positive/HER2-negative MBC aged ≥ 65 years: 1141 patients treated with the combination strategy and 950 on endocrine therapy alone (Table 1).

• Overall, the meta-analysis showed a PFS advantage of the experimental arms compared to the control arms (HR 0.77, 95%CI 0.62-0.95, p 0.016), with a significant high/moderate heterogeneity (I2 _{465.46%, p 0.005) (Figure 1).}

• Considering the 4 trials with CDK 4/6 inhibitors, a statistically significant improvement in PFS for CDK4/6 inhibitors plus ET versus ET alone (HR 0.57, 95%CI 0.45-0.71, p 0.0001) was detected (Figure 2).

• Taken singularly the other 4 trials (SWOG, FACT, HORIZON and LEA) no significant difference in PFS between ET and experimental strategies was found. • Safety profile of CDK 4/6 inhibitors in older patients was consistent with

previous findings in the overall population included in the clinical studies.

• Overall, in the subgroup of patients >65 years, combined endocrine strategies showed an improvement in PFS as first line treatment in MBC as compared to ET alone.

• The magnitude of PFS benefit due to addition of CDK 4/6 inhibitors to ET is age-independent.

• No age-based differences in safety of CDK 4/6 inhibitors were noted in clinical studies.

Background

Omarini Claudia

_{, Sperduti Isabella}

_{, Barbolini Monica}

_{, Isca Chrystel}

_{, Bocconi Alessandro}

_{, Toss Angela}

_{, Cortesi Laura}

_{, Barbieri Elena}

_{, Piacentini Federico}

_{, Cascinu Stefano}

_{, Luca Moscet}

1

_{Department of Oncology, University Hospital of Modena, Italy;}

_{Bio-statistics Unit, IRCCS Regina Elena National Cancer Istitute Roma, Italy}

The present meta-analysis aimed to understand the benefit of the new endocrine approaches as first line treatment in the subgroup of elderly patients (aged ≥65 years) with HR-positive/HER2-negative MBC

Aim

Methods

Results

Conclusions

Table 1 Characteristics of clinical trials included in the analysis

Figure 1 Meta-analysis of the PFS HRs for the subgroup Elderly patients of the 8 trials included Figure 3.Meta-analysis of the HRs of Adverse events that occurred in at least 15% of elderly patients enrolled in CDK 4/6 inhibitors trials

Abstract N: 1240

Mehta et al. NEJM 2012, 367:435-44 - Martin et al. J Clin Oncol 2015, 33:1045-1052 -

Bergh et al. J Clin Oncol 2012, 30:1919-1925 - Wolff et al. J Clin Oncol 2013, 31:195-202 - Hortobagyi et al. NEJM 2016, 375:1738-48 - Finn et al. NEJM 2016, 375:1925-36 - Finn et al. Lancet Oncol. 2015, 16:25-35 - Goetz et al. J Clin Oncol 2017, 35:3638-3646

*Data of palbociclib included all Paloma trials

References

For information: claudia.omarini@gmail.com