Background

We assumed that a strategy with dual blockade of T+P without chemotherapy followed by T-DM1 at progression might be similarly effective in terms of overall survival (OS), but less toxic resulting in better Quality of Life (QoL) in pts with HER2+ MBC. Updated efficacy results by hormone receptor (HR) status and QoL data are given.

Methods

Pts with centrally confirmed HER2+ MBC were randomized 1:1 to receive either P+T alone (arm A) or P+T combined with weekly paclitaxel or vinorelbine (arm B), followed by maintenance treatment with T+P until progression. After progression, T-DM1 was given as 2nd line therapy in both arms. The primary endpoint was OS at 24 months (mo), among secondary endpoints progression free survival (PFS) was included. QoL was assessed every 3 mo up to 24 mo during 1st line by the NFBSI-16 (summary score and subscale scores for disease-related symptoms, treatment side-effects, function/well-being). Two single items assessed treatment burden and coping.

Results

Between 05/13 and 01/16, 210 pts were enrolled. Median age was 58 years, 63% of pts had lung or liver metastases, 36% of tumors were HR-, paclitaxel/vinorelbine was given in 46/59 pts. Efficacy results are shown in table. No difference in OS was observed. HR status did not affect PFS for 1st line. During 1st line, changes from baseline showed small improvements in QoL (NFBSI-16 summary scores) in arm A, while QoL scores remained stable in arm B. Patients in arm B reported more treatment burden during the first 6 months, but not thereafter, while coping improved clinically relevant in both arms.

Table: 150O

Efficacy results

Conclusions

Despite shorter 1st line PFS, OS at 2 years was not affected for P+T alone followed by T-DM1. Side-effects were less frequently seen in the chemotherapy-free arm, although QoL was similar during 1st line in both arms.

Legal entity responsible for the study

SAKK.

Funding

Roche Pharma.

Disclosure

J. Huober: Honorary: Roche, Novartis, Lilly, Pfizer, Celgene; Advisory boards: Roche, Novartis, Lilly, Pfizer, Celgene, AstraZeneca. B. Thürlimann: Consulting or advisory role: Roche. H. Bonnefoi: Travel grants, lecture fee: Roche. All other authors have declared no conflicts of interest.

Background

CR1447 is a novel transdermal formulation of 4-OH-Testosterone with aromatase inhibiting properties and androgen receptor modulation. Phase I data demonstrated efficacy and a favorable toxicity profile. In this trial efficacy and toxicity cohort A (A) with estrogen-receptor positive disease and cohort B (B) with androgen-receptor positive triple negative metastatic breast cancer was investigated.

Methods

Based on the phase I data, a dose of 400 mg was topically administered on both thighs every day. Primary endpoint was disease control rate at week 24 (DC24). The goal is to show that disease control at 24 weeks (DC24) of > 30% (A) and >15 % (B). In (A) patients (pts) with a maximum of one line of endocrine therapy for advanced disease (AD) for at least six months without progression were eligible (N = 21). Eight pts were excluded because they did not fulfill these criteria. In (B) up to two prior lines of chemotherapy for AD were allowed.

Results

After registration of 37 pts (A)=29 and (B)=8, accrual was stopped after an interim analysis due to futility in (A) and slow accrual in (B). DC24 was reached in 5 out of 21 eligible pts (24%) in (A) and 0% in (B). In (A) eight pat were ineligible due to amendment of inclusion criteria. In (A) median PFS of eligible pts was 5.1 months (m) (95% CI: 2.5-5.6) and 2.6 months (95% CI: 2.1-2.9) in non-eligible pts. In (B) median PFS was 2.5 m (95% CI 0.7-2.6). Median OS of eligible pts in (A) was 24.6 m (95% CI 22.9-NA) and in (B) 10.8 m (95% CI 3.3-10.9). QoL assessed by FACT-ES questionnaire at baseline, week 4 and 24 showed no deterioration under treatment. CR1447 had a favorable safety profile without treatment related grade 3-5 toxicities in stratum A. Most common treatment related toxicities were: hypertriglyceridemia (60%), aspartate aminotransferase increased (51%) and dry skin (46%).

Conclusions

CR1447 is an innovative endocrine therapy with a favorable safety profile. Despite not reaching the primary endpoint (DC24 in 30% of patients), the DC24-rate of 24% in the 2^nd-line setting and one patient in prolonged PR are a signal of activity. Further evaluation in a truly endocrine sensitive population is warranted.

Clinical trial identification

NCT02067741.

Legal entity responsible for the study

SAKK Switzerland.

Funding

Curadis, Erlangen, Germany.

Disclosure

All authors have declared no conflicts of interest.