Selezionare: Il punto di vista dell’oncologo coincide con quello del “payer”?

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CARCINOMA MAMMARIO E I CDK 4/6 INHIBITORS.

Selezionare: il punto di vista dell’oncologo coincide con quello del «payer»?

Mirco Pistelli

Clinica di Oncologia Medica A. O. U. Ospedali Riuniti Ancona

Foligno, 2 marzo 2018

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• Consider MBC as a chronic disease

• Use as many therapeutic options as possible to keep an efficacy/toxicity balance as long as possible

Metastatic Breast Cancer (MBC)

Optimal Decision Making

Treatment goals in different disease settings

Terminal BC Palliation

MBC

“Chronicization”

Early BC Disease eradication

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• Cambiano davvero la pratica clinica?

CDK 4/6 INHIBITORS: il punto di vista dell’oncologo

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HER2-negative MBC: Aims of therapy

THERAPY

prevention of complications

relief of symptoms

Cure?

Increased survival

QoL

improvment

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Palliative effect of chemotherapy: Objective tumor response is associated with symptom improvement

Geels et al, JCO 18:2395, 2000

0 50 100

Pain M ood

CR/PR SD PD

Proportion of patients with symptom response according to response to chemotherapy

SOB Depression

%

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MONALEESA-2: CBR in patients with measurable disease:

80% ribociclib arm vs. 72% placebo arm (p=0.02) PALOMA-2: CBR in patients with measurable disease:

84% palbociclib arm vs. 71% placebo arm (p=0.003)

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PALOMA 3 PALBO+FULV FULV

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ER+ HER2- MBC and chemotherapy

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HER2-negative MBC: Aims of therapy

THERAPY

Cure?

QoL

improvment

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HER2-negative MBC: Aims of therapy

THERAPY

Cure?

QoL

improvment

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• Cambiano davvero la pratica clinica? SI

• Come selezionare?

CDK 4/6 INHIBITORS: il punto di vista dell’oncologo

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Benefit extended to all clinically

defined subgroups

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Benefit extended to all biologically

defined subgroups

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• Cambiano davvero la pratica clinica?

SI

• Come selezionare?

-Setting di trattamento (AI sensitive vs AI resistant)

CDK 4/6 INHIBITORS: il punto di vista dell’oncologo

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C’E’ UN VANTAGGIO NEL TRATTARE LE PZ UP-FRONT?

O MEGLIO LA SEQUENZA (OTOT+CDK 4/6)?

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Llombart-Cussac A et al, The Breast 2014

Primary vs Acquired Resistance: Prognosis

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CDK 4/6 INHIBITORS:

hanno un ruolo nella resistenza primaria? (1)

PALOMA 3

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CDK 4/6 INHIBITORS:

hanno un ruolo nella resistenza primaria? (2)

MONARCH 2

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SI

-Setting di trattamento (AI sensitive vs AI resistant) (dati controversi Ormonoresistenza primaria) -Precedente terapia ormonale

CDK 4/6 INHIBITORS: il punto di vista dell’oncologo

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MONALEESA-2: Analyses in

patients by prior (neo)adjuvant ET

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CI, confidence interval; ET, endocrine therapy; L, letrozole; NR, not reached; P, placebo; PFS, progression-free survival; R, ribociclib.

1. Conte P et al. SG-BCC 2017; abstr P141 (poster).

• Ribociclib + letrozole significantly increased PFS vs placebo + letrozole both in patients who had received prior (neo)adjuvant ET (hazard ratio=0.538; 95% CI: 0.384–0.754) and in those without prior (neo)adjuvant ET (hazard ratio=0.570; 95% CI: 0.380–0.854)

– In patients with prior (neo)adjuvant ET, median PFS was 19.3 vs 13.0 months in the ribociclib + letrozole vs placebo + letrozole arm

– In patients without prior (neo)adjuvant ET, median PFS was NR vs 19.2 months, respectively

• Ribociclib + letrozole was generally well tolerated regardless of prior ET, with similar safety profiles to that observed in the full population

Prior ET No Prior ET

R + L n=175

P + L n=171

R + L n=159

P + L n=163

Events, n 55 88 38 62

Hazard ratio (95%

CI) 0.538 (0.384–0.754) 0.570 (0.380–0.854)

100

80

60

40

20

0

0 4 8 12 16 20 24

Probability of PFS (%)

Time (Months)

Prior ET (n=346) No prior ET (n=322)

Prior ET No Prior ET

R + L n=175

P + L n=171

R + L n=159

P + L n=163

Events, n 55 88 38 62

Hazard ratio (95%

CI)

0.538 (0.384–0.754)

0.570 (0.380–0.854)

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SI

-Carico di malattia (viscerale vs non viscerale)

CDK 4/6 INHIBITORS: il punto di vista dell’oncologo

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Post hoc interaction test p<0.01

A circle represents a censored observation

Without visceral disease With visceral disease

HR 0.59 (95% CI 0.42, 0.84)

Median PFS

Fulvestrant: 22.3 months Anastrozole: 13.8 months

Proportion of patients alive and progression-free

Time (months) 0.9

1.0

0.7 0.8

0.5 0.6

0.3 0.4

0.1 0.0 0.2

Proportion of patients alive and progression-free

Time (months) 0.9

1.0

0.7 0.8

0.5 0.6

0.3 0.4

0.1 0.0

0 5 10 15 20 25 30 35 40 0.2

0 5 10 15 20 25 30 35 40

HR 0.99 (95% CI 0.74, 1.33)

Median PFS

Fulvestrant: 13.8 months Anastrozole: 15.9 months

Fulvestrant (n=135) Anastrozole (n=119) Fulvestrant (n=95)

Anastrozole (n=113)

Prima linea ormono-naive: AI vs FULVESTRANT

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Pooled analysis 749 ABC pts with ET +/- Bev.

40% had de novo ABC and 60% recurrent disease

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SI

- Carico di malattia (viscerale vs non viscerale) -Presenza di sintomi (non crisi viscerale)

CDK 4/6 INHIBITORS: il punto di vista dell’oncologo

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SI

- Carico di malattia (viscerale vs non viscerale) - Presenza di sintomi (non crisi viscerale)

- Safety/Comorbidità/Compliance/Interazioni farmaci

CDK 4/6 INHIBITORS: il punto di vista dell’oncologo

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P

P R

R

A

P Palbociclib R Ribociclib A Abemaciclib

P P

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P R P

P Palbociclib R Ribociclib

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Ca Mammario Metastatico

Miglioramento della Sopravvivenza nel tempo

Giordano S, et al. Cancer 2004

Months

60 48

36 24

12 0

Cumulative survival ^0.8

0.6

0.4

0.2

0.0

1995–2000 1990–1994

1985–1989

1980–1984

1974–1979

2000-2020??