Abstract P5-14-03: A network meta-analysis of fulvestrant 500 mg versus alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer

Introduction: Integration of patient preferences into shared decision making improves disease-related outcomes, but such data from patients with advanced breast cancer (aBC) are limited. The objective of this study was to demonstrate the relative importance of overall survival (OS) and progression-free survival (PFS) in relation to quality of life (QoL) and therapy-associated side effects from the perspective of patients with aBC. Methods: Postmenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative aBC receiving first- or second-line treatment were recruited throughout Germany. Patient-relevant attributes for aBC therapy assessment were collected using a stepwise multimodal approach. A conjoint matrix was developed, resulting in 2 attributes for therapy goals (OS and PFS), 4 for QoL, and 6 for side effects. An online quantitative survey was then performed using adaptive choice-based conjoint (ACBC) methodology. Results: The quantitative survey included 104 patients: 67 (64.4%) receiving first-line treatment and 37 (35.6%) receiving second-line treatment. The QoL attribute “physical agility and mobility” received the highest utility score (19.4 of 100%), reflecting the greatest importance to patients, followed by treatment goals (OS [15.2%] and PFS [14.4%]). Therapy-related side effects were less important, with nausea/vomiting being the most important (9.3%), followed by infection (6.4%) and hair loss (5.0%). The McFadden pseudo R2 (0.805), the root likelihood (0.864), and the χ2 test (2,809.041; p < 0.0001) indicated a very good fit of the statistical model. Conclusion: Using ACBC analysis, it appears that QoL, OS, and PFS are most important to postmenopausal patients with aBC in relation to cancer treatment. Side effects seem to be less important if OS or PFS are prolonged and the QoL is maintained. Thus, QoL, OS, and PFS should be considered equally when making treatment decisions in aBC.

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Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2016.67.3061 ◽

2016 ◽

Vol 34 (25) ◽

pp. 2961-2968 ◽

Cited By ~ 336

Author(s):

Charlotte Fribbens ◽

Ben O’Leary ◽

Lucy Kilburn ◽

Sarah Hrebien ◽

Isaac Garcia-Murillas ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Advanced Breast Cancer ◽

Metastatic Breast ◽

Advanced Breast ◽

Phase Iii ◽

Wild Type ◽

Estrogen Receptor Positive ◽

Esr1 Mutations ◽

The Impact

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

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Effectiveness and safety of eribulin in Japanese patients with HER2-negative, advanced breast cancer: a 2-year post-marketing observational study in a real-world setting

Investigational New Drugs ◽

10.1007/s10637-019-00890-5 ◽

2020 ◽

Vol 38 (5) ◽

pp. 1540-1549

Author(s):

Kenichi Inoue ◽

Masato Takahashi ◽

Hirofumi Mukai ◽

Takashi Yamanaka ◽

Chiyomi Egawa ◽

...

Keyword(s):

Breast Cancer ◽

Observational Study ◽

Confidence Interval ◽

Advanced Breast Cancer ◽

Advanced Breast ◽

Line Treatment ◽

Second Line ◽

Treatment Groups ◽

Post Marketing ◽

Grade 3

Summary Background Data on eribulin as the first- or second-line treatment in a clinical setting, especially the overall survival (OS) of patients, are scarce. Therefore, we assessed the effectiveness and safety of eribulin as the first-, second-, and third- or later-line treatments in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in Japan. Methods This multicenter, prospective, post-marketing, observational study enrolled patients from September 2014 to February 2016 in Japan and followed them for 2 years. Patients were categorized by eribulin use into the first-, second-, and third- or later-line treatment groups. Results Of 651 registered patients, 637 patients were included in the safety and effectiveness analysis. In all, first-, second-, and third or later-line treatment groups, median OS (95% confidence interval) were 15.6 (13.8–17.6), 22.8 (17.3–31.0), 16.3 (12.4–19.9), and 12.6 (11.2–15.1) months and time to treatment failure (TTF) (95% confidence interval) were 4.2 (3.7–4.4), 5.2 (3.7–5.9), 4.2 (3.7–5.1), and 3.8 (3.5–4.2) months, respectively. Prolonged TTF was associated with complications of diabetes and the development of peripheral neuropathy after eribulin treatment, according to multivariate Cox regression analysis. Grade ≥ 3 adverse drug reactions (ADRs) were reported in 61.7% of the patients. Neutropenia (49.5%) was the most common grade ≥ 3 ADR in all groups. Conclusions The effectiveness and safety results of eribulin as the first- or second-line treatment were favorable. Thus, these suggest eribulin may be a first-line treatment candidate for patients with HER2-negative advanced breast cancer in Japan.

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The efficacy of sequential second-line endocrine therapies (ETs) in postmenopausal estrogen receptor-positive and HER2-negative metastatic breast cancer patients with lower sensitivity to initial ETs

Breast Cancer ◽

10.1007/s12282-020-01095-y ◽

2020 ◽

Vol 27 (5) ◽

pp. 973-981

Author(s):

Takayuki Iwamoto ◽

Tomomi Fujisawa ◽

Tadahiko Shien ◽

Kazuhiro Araki ◽

Kentaro Sakamaki ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Metastatic Breast ◽

Lower Sensitivity ◽

Second Line ◽

Breast Cancer Patients ◽

Estrogen Receptor Positive ◽

Postmenopausal Estrogen

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Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.11.2722 ◽

1995 ◽

Vol 13 (11) ◽

pp. 2722-2730 ◽

Cited By ~ 130

Author(s):

B L Weber ◽

C Vogel ◽

S Jones ◽

H Harvey ◽

L Hutchins ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Single Agent ◽

Objective Response ◽

Advanced Breast ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy

PURPOSE We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.

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