VALOR AÑADIDO

DE LA QUIMIOTERAPIA

EN EL TRATAMIENTO DEL CNMP

ROSARIO GARCÍA CAMPELO

SERVICIO DE ONCOLOGÍA MÉDICA

HOSPITAL UNIVERSITARIO A CORUÑA

EVOLUTION OF LUNG CANCER

CLASSIFICATION OVER TIME

M Reck, DF Heigener, T Mok, JC Soria, KF Rabe, 2013

WHAT SHOULD WE DO AND WHY? In practice, quality usually means adherence to

evidence-based guidelines

BSC

Platinum-based

combinations

Single agent

chemotherapy

Gemcitabine,

vinorelbine, or

taxanes

Poor PS (PS≥2)

Carboplatin

+ paclitaxel

or

pemetrexed

ESMO guidelines*

EGFR TKI

(erlotinib)

EGFR mut+

EML4-ALK/EGFR mut+

Crizotinib

EML4-ALK+

EGFR TKI

(gefitinib)

*Category 1 and 2a recommendations

Platinum-based

combination therapy

Diagnosis

Cisplatin

(I,B)

Advanced NSCLC

Non-squamous histology

EML4-ALK-WT /EGFR WT or unknown

Pemetrexed

(II,B) Bevacizumab

+

platinum

based

regimen

(I,A)

Good PS (PS 0–1)

Adapted from NSCLC ESMO Guidelines

Peters, et al. Ann Oncol 2012

Source: Ipsos Oncology Monitor 2011 – Q3 2013 (Moving Annual Totals) – Projected Data, Excludes Clinical Trials.

78%

20%

41%

30%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

% Patients Tested

EGFR - Non-Squamous EGFR - Squamous ALK - Non-Squamous

ALK - Squamous KRAS - Non-Squamous KRAS - Squamous

% Pts Tested Q1’09 Q2‘09 Q3‘09 Q4‘09 Q1’10 Q2‘10 Q3‘10 Q4‘10 Q1'11 Q2'11 Q3'11 Q4'11 Q1'12 Q2'12 Q3'12 Q4'12 Q1'13 Q2'13 Q3'13

EGFR- Squamous 5% 4% 3% 3% 4% 5% 10% 14% 18% 22% 22% 21% 20% 19% 18% 18% 18% 19% 20% EGFR- Non-Squamous 7% 6% 6% 7% 11% 18% 31% 43% 50% 57% 60% 61% 64% 67% 70% 73% 75% 76% 78%

ALK- Squamous - - - - - - - - - 0% 4% 5% 5% 5% 5% 6% 6% 7% 8% ALK- Non-Squamous - - - - - - - - - 12% 10% 13% 14% 16% 20% 24% 31% 36% 41%

KRAS –Squamous - - - - - - - - - - 5% 5% 5% 5% 5% 5% 6% 6% 6% KRAS- Non-Squamous - - - - - - - - - - 14% 14% 14% 17% 20% 22% 26% 28% 30%

Evolution of the ALK Testing and EGFR Testing across Histologies

Source: Ipsos Oncology Monitor 2011 – Q3 2013 (Moving Annual Totals) – Projected Data, Excludes Clinical Trials.

% Pts Tested Q3'11 Q4'11 Q1'12 Q2'12 Q3'12 Q4'12 Q1'13 Q2'13 Q3'13

EGFR - Squamous 50% 54% 52% 45% 39% 35% 35% 38% 43%

EGFR - Non-Squamous 73% 74% 76% 77% 79% 81% 80% 81% 80%

ALK - Squamous 5% 4% 3% 3% 2% 1% 2% 3% 9%

ALK - Non-Squamous 4% 5% 6% 8% 12% 13% 17% 23% 29%

KRAS - Squamous 8% 8% 6% 4% 5% 7% 8% 8% 11%

KRAS - Non-Squamous 8% 8% 7% 7% 10% 11% 11% 13% 13%

Summary Overview of the SPANISH Biomarker Testing dynamics across Histologies

Molecular testing is guiding the selection

of treatment in advanced NSCLC

Kris M, et al. WCLC 2013

To date the actual implementation of

personalized medicine into oncology remains

the exception, rather than the rule in most

clinical settings.

THE GOAL OF CHEMOTHERAPY IN NSCLC

Cure…curing cancer is unrealistic for most patients

Prolong survival

Palliative symptoms

GUIDELINE ADHERENCE

Wang et al. Am J Manag Care. 2013

Which are the main factors when selecting

therapy for advanced NSCLC patients?

1. Physician Experience

2. Available Literature

3. Toxicity profile

4. Cost

5. Patient preference

Pater RB, J Clin Oncol 1995

¿Cuál es su opinión respecto al beneficio que aporta la

quimioterapia en pacientes con CNMP estadio IV?

1. Muy significativo

2. Moderado beneficio

3. Escaso beneficio

4. Nulo beneficio

5. Cualquier beneficio se ve superado por la toxicidad del tratamiento

PERSONAL BELIEFS

AND EXPERIENCE

Jennens R et al. Chest 2004

Stinchombe T et al. J Thorac Oncol 2007

VALUE ADDED refers to "extra" feature(s) of

an item of interest (product, service, person

etc.) that go beyond the standard

expectations and provide something "more"

WHAT IS VALUE IN HEALTH CARE?

Main consensus ASCO 2013

“OS endpoint is important”

• OS is a feasible endpoint, though the OS

benefit may be clouded by subsequent

therapies

• Clinical trials should aim to improve OS by

>25%

ASCO stress the use of OS endpoint. Agents hardly expected to provide such OS gain would be no longer needed in clinical practice

http://www.asco.org/practice-research/clinically-meaningful-outcomes

OVERALL SURVIVAL

2 YEARS SURVIVAL RATE NSCLC

0%

5%

10%

15%

20%

25%

30%

35%

40%

ECOG1594 JMBD ECOG4599 PARAMOUNT AVAPERL

11%

19% 23%

32%

39%

Schiller J, N Engl J Med 2002; Scagliotti, G. V. et al. J Clin Oncol 2008; Cappuzzo F et al. Lancet Oncol 2010; Ciuleanu TE et al. Lancet 2009; Paz Ares L et al. J Clin Oncol 2013; Barlesi et al. Ann Oncol 2014

Y EN PACIENTES CON

ALTERACIONES MOLECULARES...

LUCES Y SOMBRAS DE LA

MEDICINA PERSONALIZADA

BEYOND:

QT in EGFR Mut+ patients

PF

S (

pri

ma

ry e

nd

po

int)

1.0

0.8

0.6

0.4

0.2

0.0

0 5 10 15 20 Study month

7.9 12.4

Zhou, et al. WCLC 2013

Carbo/Pac + Pl: EGFR Mut+

Carbo/Pac + Bev: EGFR Mut+

A total of 152 patients contributed tissue for biomarker analysis (n=85 Carbo/Pac + Bev; n=67 Carbo/Pac + Pl)

EGFR mut-pos rate was 27% in Carbo/Pac + Bev and 25% in Carbo/Pac + Pl patients

RESPONSE RATE

TO CHEMOTHERAPY IN EGFR MUTANT

Study Control arm Ethnicity

LUX-lung 3 (n=345)

Afatinib vs Cis/pem

Asian (71%) Caucasian

LUX-LUNG 6 (n=364)

Afatinib vs Cis/Gem Asian

EURTAC (n=174)

Erlotinib v Cis/CBDCA+ Gem/Docetaxel

Caucasian

OPTIMAL (N165)

Erlotinib v Carb/Gem

Asian

WJTOG (n=172)

Gefitinib v Cis/Doc

Asian

NEJ002 (n=230)

Gefitinib v Carb/pacl

Asian

IPASS (n=261)

Gefitinib v Carb/pacl

Asian

SIGNAL (n=42)

Gefitinib Cis/Gem

Asian

Costa et al. J Clin Oncol 2012 Abstr 7523

Mujer 53 años

No fumadora

Dx en Junio 2013

Adenocarcinoma de

pulmón cT3N3M1a

Mut Exon 20

Lee et al. JTO 2011

Any CT in ALK+ patients?

65.7

29.3

6.9

Crizotinib (n=172c)

Pemetrexed (n=99c)

Docetaxel (n=72c)

40

0

Shaw A, et al. NEJM 2013

9.1

Hanna et al. JCO 2005

8.8

TENGO UNA MUTACIÓN KRAS…

Varón de 52 años, fumador de 50 paq/año

Dx en Octubre 2013 Adenocarcinoma de Pulmón, estadio IIIB/IV, EGFR WT, EML4-ALK negativo

Progresión a doblete de platino

ROS1 negativo, BRAF negativo

Kras mutado codon 12

Metro G, et al. Clin Lung Cancer 2014

Macerelli M et al. Lung Cancer 2014

245 advanced NSCLC. 15.9% LTS

① PS 0-1 at the first progression of the tumor

② Normal LDH levels at diagnosis

③ TTP > 3 months

④ Use of maintenance therapy

⑤ Number of chemotherapy agents received

⑥ Surgical resection (median survival 3.8 y)

Giroux Leprieur et al. Respirology 2012

LINES OF SYSTEMIC LINES AND OVERALL SURVIVAL

Reinmuth et al. Respiratory Oncology 2013

LOCAL THERAPY IN ADVANCED NSCLC

WHERE IS LOCAL THERAPY IN RELAPSED NSCLC WITHOUT GENETIC

ALTERATIONS?

Varón de 53 años, fumador de 60 paq/ año

En Julio 2010: Lobectomía sup derecha y linfadenectomía mediastínica mediante VATS derecha

Adenoca mixto con focos de diferenciación escamosa y neuroendocrina pT1N0M0. Ck7+ TTF1+

En Seguimiento hasta Diciembre 2011: progresión ósea, pulmonar, mediastínica y renal

EGFR WT, EML4-ALK negativo

RT paliativa sobre C5-C6

Inicia CDDP+Pem alcanzando RP a las 4 ciclos

Pem mantenimiento 20 ciclos

Mayo 2013: PE renal derecha, dolor en fosa renal y hematuria

TRAS 19 CICLOS DE PEMETREXED MANTENIMIENTO

FOLLOWING THE GUIDELINE

¿Cuál sería el valor añadido de un tratamiento de segunda línea

en términos de supervivencia libre de progresión?

1. 6 meses

2. 8 meses

3. 2-3 meses

4. 5 meses

5. 9 meses

Nefrectomía radical derecha en Julio 2013 vía

laparoscópica

METÁSTATIS DE UN CARCINOMA NEUROENDOCRINO DE ALTO GRADO, CONCORDANTE CON ORIGEN PULMONAR, DE 5,5 CM. DE DIÁMETRO MÁXIMO, QUE INFILTRA PARÉNQUIMA RENAL, PELVIS RENAL Y GRASA DEL HILIO RENAL.

NO EVIDENCIA DE PROGRESIÓN…

Marzo 2014

27 meses después de la progresión sistémica

THE TRUE ADDED VALUE…

Making progress in the value framework requires real teamwork, which sometimes seems an unnatural

act in health care.

The value framework thus makes enormous demands for cultural and organizational change among health

care providers.

Michael Porter. NEJM 2010

So, in summary…

I do believe we know much more about NSCLC cancer than some years ago: Tumors can now be defined by molecular drivers

And although I do believe is time to significantly raise the bar…superstars in oncology are the exception…progress in oncology is incremental

Chemotherapy still has a role in this new era of personalized medicine

Although following guidelines is highly recommended…

Lung Cancer is a life-threatening disease: access to potential active drugs and potential active therapeutic options is critical

SOME MYTHS…

Value added only applies to complex products.

All customers are value added targets

Value added selling is a LOT of extra work.