MONARCH 2: overall survival of Abemaciclib plus Fulvestrant in patients with HR+, HER2- advanced breast cancer


Abemaciclib ( Verzenios ) is an oral, selective cyclin-dependent kinase 4 & 6 inhibitor, approved for hormone receptor-positive ( HR+ ), human epidermal growth factor receptor 2-negative ( HER2- ) advanced breast cancer ( ABC ) as monotherapy for endocrine refractory disease and with endocrine therapy for initial treatment and after progression on endocrine therapy.

In the MONARCH 2 trial, Abemaciclib + Fulvestrant significantly improved progression-free survival ( PFS ) compared to placebo + Fulvestrant ( median: 16.4 m vs 9.3 m; hazard ratio, HR: 0.553 ) with a generally tolerable safety profile.

Researchers have reported the overall survival ( OS ) results of the prespecified interim.

MONARCH 2 was a global, randomized, double-blind phase 3 trial of Abemaciclib + Fulvestrant or Placebo + Fulvestrant in pre- or perimenopausal ( with ovarian suppression ) and postmenopausal women with advanced endocrine therapy resistant HR+, HER2- advanced breast cancer.
669 patients were randomized 2:1, stratified based on site of metastasis ( visceral, bone-only, or other ) and resistance to prior endocrine therapy ( primary vs secondary ).
Abemaciclib or Placebo 150 mg was dosed Q12H, and Fulvestrant 500 mg was administered per label.

The primary objective was investigator-assessed progression-free survival. Overall survival ( OS ) was a gated secondary endpoint.

The boundary p-value for the interim analysis was 0.0208.

At the prespecified interim analysis, 338 deaths ( 77% of the planned 441 events ) were observed in the ITT population with a median overall survival of 46.7 months for Abemaciclib + Fulvestrant and 37.3 months for Placebo + Fulvestrant ( HR: 0.757; 95% CI: 0.606, 0.945; P = 0.0137 ).

These results met the predefined boundary for significance and are thus definitive.

Overall survival benefit was consistent in all stratification factors; among stratification factors, more pronounced effects were observed in subgroups of visceral disease ( HR: 0.675 ) and primary resistance to prior endocrine therapy ( HR: 0.686 ).

PFS2 ( HR: 0.675; 95% CI: 0.558, 0.816 ) and time to chemotherapy ( HR: 0.622; 95% CI: 0.499, 0.775 ) were also significantly improved.

Safety data were consistent with known Abemaciclib safety profile.

In conclusion, treatment with Abemaciclib plus Fulvestrant has provided a statistically significant and clinically meaningful median overall survival benefit of 9.4 months to pre- or perimenopausal and postmenopausal patients with HR+, HER2- advanced breast cancer who progressed on endocrine therapy with no new safety signals observed. ( Xagena )

Source: ESMO ( European Society of Medical Oncology ) Meeting, 2019

XagenaMedicine_2019



Indietro

Altri articoli

Human papillomavirus ( HPV ) causes nearly all cervical cancers and some cancers of the vagina, vulva, penis, anus, and...


In an extensive data mining analysis of British medical records, researchers at the Johns Hopkins Kimmel Cancer Center have concluded...


The European Commission has approved Tecentriq ( Atezolizumab ) plus chemotherapy ( Abraxane [ Paclitaxel protein-bound particles for injectable suspension...


The Food and Drug Administration ( FDA ) has approved Nubeqa ( Darolutamide ) for non-metastatic castration-resistant prostate cancer. Approval was...


The phase 3 KEYNOTE-522 trial investigating Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, in combination with chemotherapy has met one...


The first prospective, longitudinal study investigating treatment of chronic hepatitis C with direct-acting antivirals finds that the treatment is associated...


Hyperprogressive disease ( HPD ) is a paradoxical boost in tumour growth described in a subset of cancer patients treated...


The first-line treatment with Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, in combination with chemotherapy has demonstrated improvements in overall...


A subset of patients treated with immune checkpoint inhibitors experience an accelerated tumor growth rate ( TGR ) in comparison...


Diabetes confers a greater excess risk of heart failure in women than men, according to new research in Diabetologia, the...