INMUNOTERAPIA: NUEVO PARADIGMA EN LOS

TUMORES DE CABEZA Y CUELLO Dra. Lara Iglesias H.U.12 Octubre

INTRODUCCIÓN

INFORME SEOM DE EVALUACIÓN DE FÁRMACOS: NIVOLUMAB EN CÁNCER EPIDERMOIDE DE CABEZA Y CUELLO

INTRODUCCIÓN

PRESENTE

PRESENTE

2ª LÍNEA

NO estandar en tratamiento hasta

2016…

PRESENTE

CheckMate 141

R 2:1

Nivolumab 3 mg/kg IV q2w

Investigator’s Choice

• Methotrexate 40-60 mg/m² IV weekly

• Docetaxel 30-40 mg/m² IV weekly

• Cetuximab 400 mg/m² IV once, then 250 mg/m² weekly

Key Eligibility Criteria

• R/M SCCHN of the oral cavity, pharynx, or larynx

• Not amenable to curative therapy

• Progression on or within 6 months of last dose of platinum-based therapy

• ECOG PS 0–1

• No active CNS metastases

• No prior targeted therapy toward T-cell co-stimulating or immune checkpoints

Stratification factor • Prior cetuximab treatment

Primary endpoint • OS

Other endpoints • PFS • ORR • TTR • Safety • Biomarkers • Quality of life

n=240

n=121

Randomized, global, phase 3 trial of the efficacy and safety of nivolumab versus single-agent therapy of investigator’s choice in patients with R/M SCCHN (n=361)

See notes for footnotes and abbreviations

PRESENTE

CheckMate 141: Overall Survival

10

Median OS,

mo (95% CI)

HR

(97.73% CI)

P value

Nivolumab (240) 7.5 (5.5, 9.1) 0.70

(0.51, 0.96) 0.0101

Investigator’s choice (121) 5.1 (4.0, 6.0)

0 3 6 9 12 15 18

Months

Nivolumab 240 167 109 52 24 7 0

Investigator’s

choice

121 87 42 17 5 1

No. at risk

0

0

10

20

30

40

50

60

70

80

90

100

OS

(%

)

1-year OS rate

(95% CI)

36.0% (28.5, 43.4)

16.6% (8.6,

26.8)

Nivolumab

Investigator’s

choice

The estimated 6-month PFS rates were 19.7% for nivolumab and 9.9% for standard therapy

Progression-Free Survival

0 3 6 9 12 15 18

Months

Nivolumab 240 79 32 12 4 1 0

Standard Therapy

121 43 9 2 0 0

No. at Risk

0

0

10

20

30

40

50

60

70

80

90

100

Pro

gre

ssio

n-f

ree

Su

rviv

al

(%)

No. of Patients

No. of Events Median PFS mo (95% CI)

Nivolumab 240 190 2.0 (1.9–2.1)

Standard Therapy 121 103 2.3 (1.9–3.1)

Hazard ratio for death, 0.89 (95% CI, 0.70–1.13), P=0.32

Nivolumab

Standard Therapy

See notes for abbreviations

Objective Response Rate

Nivolumab (n=240)

Standard Therapy (n=121)

Objective response rate, n (%) 32 (13.3) 7 (5.8)

95% CI 9.3–18.3 2.4–11.6

Best overall response, n (%)

Complete response 6 (2.5) 1 (0.8)

Partial response 26 (10.8) 6 (5.0)

Stable disease 55 (22.9) 43 (35.5)

Progressive disease 100 (41.7) 42 (34.7)

Not determined 53 (22.1) 29 (24.0)

Time to response, mo

Median (range) 2.1 (1.8–7.4) 2.0 (1.9–4.6)

See notes for reference and abbreviations

CHANGE IN TUMOR BURDEN OVER TIME*

100

Ch

ange

Fro

m B

ase

line

in

Sum

of

Targ

et

Lesi

on

s (%

)

75

50

25

0

-25

-50

-75

-100

Weeks

Responders

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84

100

Ch

ange

Fro

m B

ase

line

in

Sum

of

Targ

et

Lesi

on

s (%

)

75

50

25

0

-25

-50

-75

-100

Weeks

Stable Disease

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84

100

Ch

ange

Fro

m B

ase

line

in

Sum

of

Targ

et

Lesi

on

s (%

)

75

50

25

0

-25

-50

-75

-100

Weeks

Responders

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84

100

Ch

ange

Fro

m B

ase

line

in

Sum

of

Targ

et

Lesi

on

s (%

)

75

50

25

0

-25

-50

-75

-100

Weeks

Stable Disease

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84

Nivolumab Standard Therapy

1st occurrence of new lesion Off treatment Time of first response

Tumor reductions were more durable with nivolumab, shown as tumor-burden plots over time for patients who had either a partial response or a complete response

See notes for footnotes

PD-L1 Baseline ≥1%

No. of Patients

No. of Deaths

Median OS mo (95% CI)

Nivolumab 88 49 8.7 (5.7–9.1)

Standard Therapy 61 45 4.6 (3.8–5.8)

88 67 44 18 6 0

61 42 20 6 2 0

73 52 33 17 8 3 0

38 29 14 6 2 0 0

Nivolumab

Standard Therapy

Nivolumab Standard Therapy

No. at Risk

Ove

rall

Surv

ival

(%

)

Nivolumab

Standard Therapy

Months 0 3 6 9 12 15 18

0

10

20

30

40

50

60

70

80

90

100

Months 0 3 6 9 12 15 18

0

10

20

30

40

50

60

70

80

90

100

Overall Survival by PD-L1 Expression

Estimates for OS HR for PD-L1 expression levels of ≥5% and ≥10% are similar to those for ≥1%

PD-L1 Baseline <1%

No. of Patients

No. of Deaths

Median OS mo (95% CI)

Nivolumab 73 45 5.7 (4.4–12.7)

Standard Therapy 38 25 5.8 (4.0–9.8)

Hazard ratio for death, 0.55 (95% CI, 0.36–0.83) Hazard ratio for death, 0.89 (95% CI, 0.54–1.45)

See notes for abbreviations

-30

-20

-10

0

10

20

30

9 15 9 15 9 15

MID

MID

Social Contact

Problems

Sensory Problems Pain

Week

P =

0.001

P =

0.258

P =

0.012

P <

0.001

P <

0.001

P =

0.022

Bett

er

Wo

rse

Me

an

Ch

an

ge

Fro

m B

as

eli

ne

(9

5%

CI)

QoL: EORTC QLQ-H&N35 Symptom Burden

15

Nivolumab Investigator's

choice

QoL: EORTC QLQ-C30 Time to Deterioration (Functioning)

• Nivolumab resulted in more than doubling of time to deterioration for most functional domains

16

Global health/QoL

Physical functioning

Role functioning

Emotional functioning

Social functioning

Cognitive functioning

0 0,5 1 1,5 2

Hazard Ratio (95% CI)

7.7 (5.4,

13.3) 3.0 (2.1, 6.1)

7.8 (6.7, NR) 3.6 (2.4, 6.3)

8.6 (5.4, NR) 3.8 (2.6, 7.6)

6.7 (5.4, NR) 4.7 (3.3, NR)

7.8 (5.6, NR) 3.3 (2.4, 6.1)

7.7 (5.4, NR) 3.0 (2.1, 4.7)

Median Time to Deterioration

(95% CI), mo

Nivo IC Favors Nivo Favors IC

Treatment related AE in ≥5% of Patients

Treatment-related adverse event rates of any grade were similar in the two groups, and fewer grade 3 or 4 events were reported in the nivolumab group than in the standard-therapy group

Event Nivolumab (n=236) Standard Therapy (n=111)

Any grade Grade 3 or 4 Any grade Grade 3 or 4

number of patients (percent)

Any event 139 (58.9)* 31 (13.1) 86 (77.5)† 39 (35.1)

Fatigue 33 (14.0) 5 (2.1) 19 (17.1) 3 (2.7)

Nausea 20 (8.5) 0 23 (20.7) 1 (0.9)

Rash 18 (7.6) 0 5 (4.5) 1 (0.9)

Decreased appetite 17 (7.2) 0 8 (7.2) 0

Pruritus 17 (7.2) 0 0 0

Diarrhea 16 (6.8) 0 15 (13.5) 2 (1.8)

Anemia 12 (5.1) 3 (1.3) 18 (16.2) 5 (4.5)

Asthenia 10 (4.2) 1 (0.4) 16 (14.4) 2 (1.8)

Vomiting 8 (3.4) 0 8 (7.2) 0

Dry skin 7 (3.0) 0 10 (9.0) 0

Stomatitis 5 (2.1) 1 (0.4) 10 (9.0) 3 (2.7)

Weight loss 4 (1.7) 0 6 (5.4) 0

Mucosal inflammation 3 (1.3) 0 14 (12.6) 2 (1.8)

Peripheral neuropathy 1 (0.4) 0 7 (6.3) 0

Alopecia 0 0 14 (12.6) 3 (2.7)

Neutropenia 0 0 9 (8.1) 8 (7.2)

See notes for footnotes

FUTURO

FUTURO 1ª Línea:

DURVALUMAB +/- TREMELIMUMAB PEMBROLIZUMAB +/- PLATINO NIVOLUMAB + IPILIMUMAB PEMBRO/NIVO + EPACADOSTAT

2ªLínea: DURVALUMAB +/- TREMELIMUMAB DURVALUMAB +/- AZD9150 ATEZOLIZUMAB

QTRT: CISPLATINO + PEMBROLIZUMAB CETUXIMAB + DURVALUMAB

INDUCCIÓN

CASO CLÍNICO

NIVOLUMAB

3ª LÍNEA (9s)

NIVOLUMAB: 3mg/kg peso basal

• RESPUESTA PARCIAL MANTENIDA a todos los niveles 2 años

EVOLUCIÓN: EFICACIA Y CALIDAD

DE VIDA

QUIMIOTERAPIA

- Platinos

- Antimetabolitos

- Taxanos

-

TERAPIAS DIRIGIDAS

- Cetuximab

- Afatinib ¿?

INMUNOTERAPIA

- Monoterapia ANTI-PD1

CONCLUSIONES

Aumentar la supervivencia de los pacientes con cáncer escamoso de cabeza y cuello

recurrente/metastásico

¡GRACIAS!

laraiglesias@hotmail.com