ESMO Pre-Research Alert| Advances in ER+/HER2-advanced/metastatic breast cancer endocrine therapy

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The 2022 European Society of Medical Oncology (ESMO) Annual Meeting was held
in Paris from September 9 to 13 local time.
Endocrine therapy is an indispensable treatment for ER+/HER2-breast cancer patients, what research results were announced at this year's ESMO conference, and what treatment options will be brought to this part of the patient?

Subgroup Analysis of the Phase 220P-III EMERALD Study: Oral Selective Estrogen Receptor Degrader (SERD) Elacestrant versus Fulvestrant or Aromatase Inhibitor (AI) Monotherapy for ER+/HER2-Advanced/Metastatic Breast Cancer (mBC)

background

The EMERALD clinical trial showed that elacestrant significantly prolonged progression-free survival (PFS) compared with standard endocrine therapy (SOC) in patients with ER+/HER2-mBC who had progressed after prior endocrine therapy and CDK4/6i inhibitor (CDK4/6i) and was tolerated
toxicity.
Benefit
in the general population and patients with ESR1 mutations (mESR1).
At the ESMO conference, researchers reported a subgroup analysis of EMERALD, comparing the efficacy
of elacestrant with fulvestrant or AI.

method

A randomized, open-label, phase III EMERALD study (NCT03778931) randomized (1:1) to receive elacestrant (400 mg/day orally) or SOC (fulvestrant or AI) in patients with ER+/HER2 mBC prior 1-2 lines of endocrine therapy, CDK4/6i pretreatment, and ≤ 1 chemotherapy, randomized (1:1) to receive elacestrant (400 mg/day orally) or SOC (fulvestrant or AI), which recommends AI therapy in patients previously treated with fulvestrant, Patients previously treated with AI were treated with fulvestrant (Figure 1).

The primary endpoint was PFS
in the whole population and in mESR1 patients.
This post-hoc analysis compared the PFS
of elacestrant with fulvestrant and the AI group.

Figure 1.
Study design

outcome

A total of 477 patients were enrolled, 239 in the elacestrant group, 238 in the SOC group, 165 (69%) patients were treated with fulvestrant (159 patients were previously treated with AI), 73 (31%) were treated with AI (69 patients were previously treated with fulvestrant), and the characteristics of the patients were similar between the two groups (Table 1).

Table 1.
Patient baseline characteristics

In the whole population and mESR1 patients, elacestrant treatment was associated with PFS prolongation at 6, 12, 15, and 18 months compared with fulvestrant or AI (Figure 2).

Figure 2.
PFS

Security is controllable
.
The most common adverse event was nausea (all grades: 35.
0% [vs.
fulvestrant 16.
1%, AI 25.
0%]; Grade 3/4: 2.
5% [vs 0% fulvestrant, 2.
9% AI]) (Table 2).

Table 2.
Adverse events

conclusion

In patients with ER+/HER2 mBC, elacestrant significantly prolonged PFS compared with fulvestrant and AI, regardless
of the type of endocrine therapy.

228P-JBCRG-M07 (FUTURE TRIAL): FULVESTRANT IN COMBINATION WITH PIPERACICILLIDE FOR ER+/HER2-ADVANCED OR METASTATIC BREAST CANCER AFTER PROGRESSION OF FULVESTRANT MONOTHERAPY

background

Fulvestrant is one of the
standard regimens for first- and second-line endocrine therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC).
This study explored whether the combination of piperiboxiclib and fulvestrant is effective and safe
in patients with HR+ MBC and advanced breast cancer (ABC) who relapse after fulvestrant therapy.

method

Patients are initially enrolled
during first- and second-line endocrine therapy with fulvestrant.
Secondary registration is performed when patients develop disease progression during fulvestrant monotherapy and receive fulvestrant in combination with piperaciclib regimen as study therapy (Figure 3).

The primary endpoint was progression-free survival (PFS)
from the start of study treatment.
Secondary endpoints included time from study treatment initiation to treatment failure (TTF) and adverse events
.

Figure 3.
Study design

outcome

Between January 2018 and February 2020, 167 patients from 55 centers were enrolled for the first time (9 were discharged because they did not meet the inclusion criteria), of which 72 patients were re-enrolled (Table 3).

Table 3.
Patient characteristics

The median follow-up time for primary and secondary enrollment was 23.
8 months and 8.
9 months
, respectively.
The median PFS of patients resistant to fulvestrant monotherapy was 9.
4 months (90% CI, 6.
9-11.
2 months, p<0.
001).

The TTF for secondary registration was 7.
2 months (90% CI, 5.
5-10.
4 months).

(Figure 4).

Figure 4.
PFS and TTF

No new adverse events were observed (Table 4).

Table 4.
Adverse events

conclusion

The results of this study suggest that piperaciclib in combination with fulvestrant may be effective and safe in the treatment of HR+/HER2-ABC/MBC patients after the progression of fulvestrant monotherapy
.

References:

1.
I.
P.
G.
Aftimo, J.
Cortés, F.
C.
Bidard, et al.
 Elacestrant vs fulvestrant or aromatase inhibitor (AI) in phase III trial evaluating elacestrant, an oral selective estrogen receptor degrader (SERD), vs standard of care (SOC) endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC): Subgroup analysis from EMERALD.
 Abstract 220P.
 Annals of Oncology (2022) 33 (suppl_7): S88-S121.
10.
1016/annonc/annonc1040

2.
K.
Watanabe, N.
Niikura, Y.
Kikawa, et al.
 Fulvestrant with additional palbociclib in advanced or metastatic hormone receptor-positive HER2-negative breast cancer after progression to fulvestrant monotherapy: JBCRG- M07 (FUTURE trial).
 Abstract 228P.
 Annals of Oncology (2022) 33 (suppl_7): S88-S121.
10.
1016/annonc/annonc1040