Versión 2 (definitiva): Presentado en la Clínica VIDA en 11.11.2016, por invitación de Jairo Estrada. Versión corregida (se corrigen errores en 3 diapositivas de la versión anterior).
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Tratamiento inicial de pacientes posmenopáusicas con cáncer de mama HR+/her2- metastásico: Una visión panorámica
1. Tratamiento inicial de cáncer de mama
en pacientes posmenopáusicas
HR+/Her2- metastásico: una visión
panorámica
Mauricio Lema Medina MD
Clínica de Oncología Astorga / Clínica SOMA, Medellín
Medellín, 11.11.2016
6. CMF vs Tam
CMF vs Tam + Androgen
FU vs Androgen
AC vs Tam
FACV vs Various
Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer
(Review)
Wilcken N, Cochrane, 2003
7. A Randomized Trial in Postmenopausal Patients With Advanced Breast
Cancer Comparing Endocrine and Cytotoxic Therapy Given
Sequentially or in Combination
ANZBCTG, JCO (1986): 4; 186-193
CR + PR + NC 76% 81% 84%
8. A Randomized Trial in Postmenopausal Patients With Advanced Breast
Cancer Comparing Endocrine and Cytotoxic Therapy Given
Sequentially or in Combination
ANZBCTG, JCO (1986): 4; 186-193
10. What is the optimal
first-line chemotherapy in aBC?
11. Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in
patients with advanced breast cancer: a phase III study conducted by the Hellenic
Cooperative Oncology Group
Fountzilas G, Ann Oncol, 2004
Paclitaxel Epirubicin
Paclitaxel Carboplatin
RMBC
327 patients
Unknown Her2 status
Both ER+ and ER- Endpoint: OS
12. Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in
patients with advanced breast cancer: a phase III study conducted by the Hellenic
Cooperative Oncology Group
Fountzilas G, Ann Oncol, 2004
Paclitaxel Epirubicin
Paclitaxel Carboplatin
RMBC
327 patients
Unknown Her2 status
Both ER+ and ER- Endpoint: OS
TTF
Paclitaxel + Carboplatin: 10.8 mo
Paclitaxel + Epirubicin: 8.1
OS
Paclitaxel + Carboplatin
Paclitaxel + Epirubicin
NS: 22-27mo
13. A randomized phase III study comparing three anthracycline-free taxane-based
regimens, as first line chemotherapy, in metastatic breast cancer
Fountzilas G, Breast Cancer Res Treat, 2009
Docetaxel + Gemcitabine q3w
Weekly paclitaxel
RMBC
416 patients
ER+: 65%
Triple negative: 15%
Trastuzumab in 6 patients
Endpoint: OS
OS
Paclitaxel + Carboplatin q3w
OS
Paclitaxel + Carboplatin: 29.9 mo
Docetaxel + Gemcitabine: 26.9 mo
Weekly Paclitaxel: 41.0 mo
p=0.037
PFS
11 mo
14. A randomized phase III study comparing three anthracycline-free taxane-based
regimens, as first line chemotherapy, in metastatic breast cancer
Fountzilas G, Breast Cancer Res Treat, 2009
15. A randomized phase III study comparing three anthracycline-free taxane-based
regimens, as first line chemotherapy, in metastatic breast cancer
Fountzilas G, Breast Cancer Res Treat, 2009
PCb vs Weekly paclitaxel
16. 2009 Weekly paclitaxel 49% 47wks75%
Fountzilas, Breast Cancer Res Treat, 2009
ORR CBR PFS/TTF
ER+/ER-/Her2+
17. What is the optimal
first-line chemotherapy in aBC?
Weekly paclitaxel appears to be
superior to combination agents in
“all-comers” with aBC
18.
19. What is the optimal
first-line single-agent hormonal
therapy in HR+/Her2- aBC?
20.
21. 2001 Tamoxifen 20% 26wks38%
Letrozole 30% 41wks49%
Mouridsen H, JCO, 2001
HR: 0.7
ORR CBR PFS/TTF
ER/PR status unknown in some
27. ESMO-2016, Copenhagen, 7-11 October 2016
A phase 3 trial confirms a phase 2 trial (FIRST).
Fulvestrant appears less effective in visceral metastases.
All patients where hormonotherapy naïve.
30. What is the optimal
first-line single-agent hormonal
therapy in HR+/Her2- aBC?
Fulvestrant is superior to AIs and
displays a remarkable OS in non-
visceral metastatic in de-novo aBC
34. Anti ER treatment with Fulvestrant induces
PI3k pathway activation
Fox EM, Arteaga CL, Miller TW. Frontiers in Oncology, 2012
35. Hortobagyi GN et al. SABCS 2011;Abstract S3-7.
Postmenopausal, ER-
positive locally
advanced or metastatic
breast cancer
Progression on letrozole
or anastrozole
(n = 724)
R
Everolimus – 10 mg daily
+
Exemestane – 25 mg daily
(n = 485)
Placebo
+
Exemestane – 25 mg daily
(n = 239)
Stratification: Sensitivity to prior hormonal therapy and presence of visceral metastases
Endpoints:
• Primary: Progression-free survival (PFS) by local assessment
• Secondary: Overall survival, overall response rate, quality of life,
safety, bone markers, pharmacokinetics
BOLERO-2 Study Design
36. Patients with primary resistance were
those relapsing during or within 6
months of stopping adjuvant AI
treatment or progressing within 6
months of starting AI treatment in the
metastatic setting
37. Response and Clinical Benefit
Everolimus + Exemestane
Placebo + Exemestane
Response Clinical Benefit
Percent
12.0%
1.3%
50.5%
25.5%
P < 0.0001
P < 0.0001
Baselga J, et al. N Engl J Med. 2012;366:520-529.
41. Bolero-2: OS of Exemestane + Everolimus
in mBC
Piccert M, et al. Ann Oncol 2014
42. 2012 Exemestane (E) 1% 17wks25%
Everolimus + E 13% 49wks50%
Baselga, NEJM, 2012
ORR CBR PFS/TTF
Progressing after neoadjuvant therapy
Central review
43. Royce, M. ESMO (2016), Abstract 2220
BOLERO-4: Phase 2 trial of first-line everolimus (EVE) plus letrozole (LET) in
estrogen receptor–positive (ER+), human epidermal growth factor receptor
2–negative (HER2−) advanced breast cancer (BC)
44. Royce, M. ESMO (2016), Abstract 2220
BOLERO-4: Phase 2 trial of first-line everolimus (EVE) plus letrozole (LET) in
estrogen receptor–positive (ER+), human epidermal growth factor receptor
2–negative (HER2−) advanced breast cancer (BC)
45. Royce, M. ESMO (2016), Abstract 2220
BOLERO-4: Phase 2 trial of first-line everolimus (EVE) plus letrozole (LET) in
estrogen receptor–positive (ER+), human epidermal growth factor receptor
2–negative (HER2−) advanced breast cancer (BC)
46. Royce, M. ESMO (2016), Abstract 2220
BOLERO-4: Phase 2 trial of first-line everolimus (EVE) plus letrozole (LET) in
estrogen receptor–positive (ER+), human epidermal growth factor receptor
2–negative (HER2−) advanced breast cancer (BC)
55. PALOMA 2: AE Summary
• Most AEs resulting in d/c reported as single events, most commonly
neutropenia with palbociclib (1.6%) or fatigue with placebo (0.9%)
• One on-study, treatment-related death because of pulmonary
embolism/respiratory failure in placebo arm
Slide credit: clinicaloptions.comFinn R, et al. ASCO 2016. Abstract 507.
Outcome, % Palbociclib +
Letrozole (n = 444)
Placebo +
Letrozole (n = 222)
Serious AE 19.6 12.6
Serious AE occurring in ≥ 1% of pts
Febrile neutropenia
Pulmonary embolism
1.6
0.9
0
1.4
AE-related discontinuation 9.7 5.9
AE-related death 2.3 1.8
56. PALOMA 2: Conclusions
• First-line palbociclib + letrozole significantly improved median PFS vs
placebo + letrozole in women with ER+/HER2- advanced breast
cancer
– Median PFS improved by > 10 mos compared to placebo
• 24.8 mos vs 14.5 mos, HR: 0.58 (95% CI: 0.46-0.72; P < .0001)
• Palbociclib clinical benefit observed in all prespecified subgroups
• Palbociclib well tolerated with neutropenia, leukopenia the most
frequently reported AEs
• PALOMA-2[1] data confirm PALOMA-1[2] results and constitute the longest
median PFS improvement to date in the front-line setting in advanced ER+
breast cancer
Slide credit: clinicaloptions.com
1. Finn R, et al. ASCO 2016. Abstract 507.
2. Finn RS, et al. Lancet Oncol. 2015;16:25-35.