09 Tratamiento combinado de quimio y radioterapia en Cáncer de Pulmón

Tratamientos locorregionales en el NSCLC

Tratamiento combinado QT/RT

B.Massutí

Hospital General Universitario Alicante

BIENVENIDA: Dra. Remei Blanco Guerrero y Dr. Jose Muñoz Langa

10:30. INTRODUCCIÓN: DE AMSTERDAM A SIDNEY

Dra. Remei Blanco

10:45. MESA I: DIAGNÓSTICO, EPIDEMIOLOGÍA Y BIOLOGÍA MOLECULAR.

Moderadores: Dr. Óscar Juan y Dra. Regina Gironés

10:45-11:05. Epidemiología, screening y prevención

Dr. Francisco Aparisi

11:05-11:25. Diagnóstico y estadificación

Dr. César Valdés

11:25-11:45. Biología molecular

Dra. Eloisa Jantús

11:45-12:00. Discusión

12:00-12:15. COFFE BREAK

12:15. MESA II: OTROS TUMORES TORÁCICOS.

Moderadores: Dr. Gaspar Esquerdo y Dr. Josep Belda

12:15-12:30. Mesotelioma y Timoma

Dra. Pilar Lianes

12:30-12:45. SCLC

Dr. Javier Garde


13:00. MESA III: TRATAMIENTOS LOCORREGIONALES EN EL NSCLC.

Moderadores: Dr. Bartomeu Massutí y Dr. Josep María Solé

13:00-13:15. Cirugía

Dr. José Galbis

13:15-13:30. Radioterapia

Dr. Luis Fernández

13:30-13:45. Tratamiento combinado: QT/RT

Dr. Bartomeu Massuti


14:00-15:00. COMIDA

15:00. MESA IV: TRATAMIENTOS SISTÉMICOS EN EL NSCLC.

Moderadores: Dra. Edurne Arriola y Dr. Alfredo Sánchez

15:00-15:15. Antiangiogénicos

Dr. Javier Pérez

15:15-15:30. Terapias dirigidas

Dr. Jordi Remón

15:30-15:45. Quimioterapia (1ª y 2ª líneas y mantenimiento)

Dra. Margarita Majem

15:45-16:00. Inumoterapia

Dr. José Muñoz Langa


16:15. CONCLUSIONES: DE SIDNEY A DENVER

Dra. Josefa Terrasa

CLAUSURA: Dra. Remei Blanco Guerrero y Dr. José Muñoz Langa

HOTEL SILKEN PUERTA VALENCIA ****Cardenal Benlloch, 28

46021-Valencia, España

Tel: +34 963 936 395

PONENTES

Dr. Francisco Aparisi.

Oncología Médica. H. Virgen de Los Lirios. Alcoi.

(Alicante)

Dra. Edurne Arriola.

Oncología Médica. H. del Mar. Barcelona

Dr. Josep Belda.

Cirugía Torácica. H. Mutua de Terrassa. (Barcelona)

Dra. Remei Blanco.

Oncología Médica. H. de Terrassa. (Barcelona)

Dr. Gaspar Esquerdo.

Oncología Médica. H. de Elda. (Alicante)

Dr. Luís Fernández.

Oncología Radioterápica. H. General de Elche. (Alicante)

Dr. José Galbis.

Cirugía Torácica. H. de La Ribera. Alzira (Valencia)

Dr. Javier Garde.

Oncología Médica. H. Arnau de Vilanova. Valencia

Dra. Regina Gironés.

Oncología Médica. H. Lluis Alcanyis. Xátiva (Valencia)

Dra. Eloisa Jantús.

Biología Molecular. H. General Universitario de Valencia

Dr. Óscar Juan Vidal.

Oncología Médica. H. UiP. La Fe. Valencia

Dra. Pilar Lianes.

Oncología Médica. H. de Mataró. (Barcelona)

Dra. Margarita Majem.

Oncología Médica. H. Sant Pau. Barcelona

Dr. Bartomeu Massutí.

Oncología Médica. H. General de Alicante

Dr. José Muñoz Langa.

Oncología Médica. H. Dr. Peset. Valencia

Dr. Javier Pérez.

Oncología Médica. H. General de Elche. (Alicante)

Dr. Jordi Remón.

Oncología Médica. H. de Mataró. (Barcelona)

Dr. Alfredo Sánchez.

Oncología Médica. H. Provincial de Castellón.

Dr. Josep María Solé.

H. General de Cataluña. Bellaterra (Barcelona)

Dra. Josefa Terrassa.

Oncología Médica. H. Son Espases. Palma de Mallorca

Dr. César Valdés.

Neumología. H. de Terrasa. (Barcelona)

HOSPITALS

DÍLLES

BALEARS

Agenda

• Situación actual y resultados terapéuticos

• Cuestiones abiertas

• Presentaciones en WCLC 2013

• Perspectivas de futuros

7th IASLC Staging System

T and M N0 N1 N2 N3

UICC6 and descriptor New

T/M Stg Stg Stg Stg

T1 (2 cm) T1a IA IIA IIIA IIIB

T1 (>2-3 cm) T1b IA IIA IIIA IIIB

T2 (5 cm) T2a IB IIA IIIA IIIB

T2 (>5-7 cm) T2b IIA IIB IIIA IIIB

T2 (>7 cm)

T3

IIB IIIA IIIA IIIB

T3 invasion IIB IIIA IIIA IIIB

T4 (same lobe

nodules) IIB IIIA IIIA IIIB

T4 (extension)

T4

IIIA IIIA IIIB IIIB

M1 (ipsilateral lung) IIIA IIIA IIIB IIIB

T4 (pleural effusion)

M1a

IV IV IV IV

M1 (contralateral

lung) IV IV IV IV

M1 (distant) M1b IV IV IV IV

7th IASLC TNM Staging System: Survival according to N status and single/multiple nodal zones

STAGE 5-year SURVIVAL

I 60 – 70%

II 40 – 55%

IIIA 10 – 25%

IIIB 5%

IV < 1%

NSCLC stages at presentation and

treatment outcomes

Approximately 10-15% of newly diagnosed NSCLC p. will be classified as stage IIIA-N2

Stage I

Stage II

Stage III

Stage IV30%

Evolución de los resultados terapéuticos tto QT/RT

• Medianas sup EC aleatorizados:

– 80´s: 9 m

– 90´s: 14 m

– 2000´s: 18 m

– 2010´s: 20 m

Metanálisis QT-RT secuencial vs concomitante / JCO 2010;38:2181-2190

Rowell N; O’Rourke N Cochrane Database Syst Rev 2004

RT vs QTRT (R.R)

Risk of death (2a) 0.93

↑PFS (LR)2a 0.84

↑ PFS 0.90

Absolute risk death 1.13

Anemia 3.19

Neutropenia 3.12

Acute esophagitis 1.58

Late esophagitis 1.72

Pneumonitis 1.19

Lung fibrosis 1.15

QTRTvs QTRT (R.R)

Risk of death (2a) 0.86

↑PFS (LR)2a 0.84

Absolute risk death 1.60

Neutropenia 1.07

Acute esophagitis 6.77

PNeumonitis 0.66

Tratamientos combinación: selección pacientes

Bajo riesgo Riesgo intermedio Alto riesgo

PS 0-1

No comorbilidades

Edad < 70 a

PFR buenas

V20<35%

PS 0-1

Pocas comorbil.

Edad < 80 a

PFR aceptables

35 < V <45%

PS >1

Comorbilidades

Cualquier edad

PFR afectadas

V > 45%

RT-QT concomitante QT-RT secuencial Tratamiento paliat.

Pacientes elegibles para tto QT/RT concomitante

Registro población de Maastricht (853.553 habitantes)

711 pacientes Estadio III (81% CPNM, 18% CPCP) (2002-2005).

Características clínicas: ◦ 545 (76.7%) < 75 años ◦ Comorbilidades: 63.1% (> 75 a) versus 47.1% (< 75 a )

Resultados: ◦ En el grupo de edad 60 – 69 a, solamente 50% se

considerarían elegibles para tto concomitante ◦ Entre 70 – 74 a, < 50% ◦ 60% de la población ineligible para tto concomitante

De Ruysscher D. Ann Oncol 2009

Cuestiones abiertas

• Secuencia QT/RT: – QT Inducción – QT Consolidación

• Esquemas QT concomitante: – Dosis plenas – Dosis frecuentes

• Dosis RT • Integración agentes biológicos • Reducción toxicidad • Estrategias inmunoterapia • Heterogeneidad estadios IIIA-IIIB

RTOG 0617: Phase III Trial of 74 Gy vs 60

Gy RT in Unresectable Stage III NSCLC

Bradley JD, et al. ASCO 2013. Abstract 7501.

*CT consisted of carboplatin/paclitaxel. †400 mg/m2 loading dose on Day 1, followed by weekly dose of 250 mg/m2

Patients with newly

diagnosed, unresectable

stage IIIA/IIIB NSCLC

(N = 464)

Stratified by RT technique,

Zubrod status, PET staging,

histology Concurrent Treatment Consolidation Treatment

Standard-Dose RT + concurrent CT*

(n = 125)

Consolidation CT*

High-Dose RT + concurrent CT*

(n = 121)

Consolidation CT*

Standard-Dose RT + concurrent CT* +

Cetuximab† (n = 108)

Consolidation CT* +

Cetuximab†

High-Dose RT+ concurrent CT* +

Cetuximab† (n = 110)

Consolidation CT* +

Cetuximab†

Primary endpoint: OS

RTOG 0617: Survival

Efficacy Outcome Standard-Dose RT

(n = 213)

High-Dose RT

(n = 206)

HR (95% CI)

P Value

Median OS, mos 28.7 19.5 1.56

(1.19-2.06) .0007

18-mo PFS, % 36.6 26.3 1.30

(1.04-1.63) .0116

18-mo local failure, %

25.1 34.3 1.37

(0.99-1.89) .0319

18-mo distant failure, %

42.4 47.8 1.15

(0.87-1.51) .1576


RTOG 0617: Safety

• Grade 3 esophagitis occurred significantly more often with high-dose vs standard-dose RT (20.9% vs 7.0%; P = .0003)

Adverse Events Definitely, Probably, or Possibly Related to Treatment, %

Standard-Dose RT

(n = 213)

High-Dose RT

(n = 206)

Worst nonhematologic events

Grade 3 46.0 46.1

Grade 4 9.9 11.2

Grade 5 0.9 4.9

Worst overall

Grade 3 46.5 41.7

Grade 4 26.8 31.6

Grade 5 0.9 4.9


Resultados

• HR PFS 0.96 (0.77-1.19)

• HR OS 0.99 (0.78-1.27)

Summary

• High-dose RT (74 Gy) associated with higher risk of death, locoregional recurrence, and incidence of fatal AEs vs low-dose RT (60 Gy) when administered with concurrent CT in patients with newly diagnosed, unresectable stage III NSCLC

• Analysis of the addition of cetuximab to high- and low-dose RT with concurrent CT is ongoing


WCLC 2013: RTOG 0716: Cetuximab analysis

- Compare the overall survival of patients treated with concurrent chemo-radiotherapy plus cetuximab versus chemo-radiotherapy alone

Toxicidades comparativas

Toxicidades Cetuximab (237 p) No Cetuximab (227 p)

Grado 3 Grado 4 Grado 5 Grado 3 Grado 4 Grado 5

No-Hematol. 130 (54.9%)

26 (11%)

11 (4.6%)

91 (40.1%) 18 (7.9%)

6 (2.6%)

Conjunto 167 (70.5%) 115 (50.7%)

Maxima toxicidad

117 (49.4%)

74 (31.2%)

11 (4.6%)

93 (41%)

57 (25.1%) 7 (3.1%)

Conjunto 202 (85.2%) 157 (69.2%)

P> 0.0001

Overall survival

Tecemotide (L-BLP25):

Novel Lipopeptide Cancer Vaccine

Adjuvant = Monophosphoryl lipid A The adjuvant supports T-cell response by inducing pro-inflammatory cytokines (via TLR4 stimulation)

Antigen = BLP25 lipopeptide The amino acids of the lipopeptide provide antigenic epitopes for T cells

MUC1 mucin

Structural lipids = cholesterol, DPPC, and DMPG Further enhancement of antigen delivery/uptake into APCs and immune reaction

G S T A P P A H G V T S A P D T R P A P

S T A P P A H G V T S A P D T R P A P G S T A P P - Lys (PAL) G

Butts CA, et al. ASCO 2013. Abstract 7500. Used with permission.

START: Study Design

Patients with unresectable

stage IIIA/B NSCLC without

disease progression following

chemoradiotherapy

(N = 1239)

Tecemotide 806 µg SC weekly for 8 wks, then every 6 wks thereafter +

Best Supportive Care (n = 829)

Placebo + Best Supportive Care

(n = 410)

Randomized 2:1; stratified by disease stage, response

to chemoradiotherapy, concurrent vs sequential chemoradiotherapy,

geographic region

Treated

until PD

1 dose of cyclophosphamide 300 mg/m2 or saline given 3 days prior to first tecemotide or placebo dose,

respectively.


L-BLP25 (n = 829)

Placebo (n = 410)

Median OS, mos 25.6 22.3

Adjusted HR 0.88 (95% CI: 0.75-1.03; P = .123*)

Median follow-up, mos 39.9 37.7

START: Overall Survival

353

757

188

429

Placebo

L-BLP25

410

829

285

617

127

301

108

255

88

204

59

128

33

73

18

33

4

8

0

0

Pts at Risk, n

Su

rviv

al (%

)


*2-sided, strata and multiplicity adjusted

Mos

L-BLP25

Placebo

100

90

80

70

60

50

40

30

20

10

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

Region

0.86 (0.67-1.11)

0.90 (0.74-1.09)

0.79 (0.58-1.09)

0.91 (0.71-1.17)

0.95 (0.73-1.22)

0.85 (0.65-1.11)

0.91 (0.75-1.10)

0.78 (0.64-0.96)

1.11 (0.86-1.43)

Favors L-BLP25

Stage IIIA (n = 487)

Stage IIIB (n = 752)

NA and Aus. (n = 321)

W. Europe (n = 475)

Rest of world (n = 443)

SD (n = 396)

Obj. response (n = 843)

Concurrent (n = 806)

Sequential (n = 433)

Stage

Response

to chemo/RT

Chemo/

RT type

Median OS, Mos

L-BLP25 vs Placebo

HR* (95% CI)

Favors Placebo *Not adjusted for strata.


START: OS Analyses by

Randomization Strata

27.6 vs 23.1

23.7 vs 20.9

34.1 vs 21.7

24.2 vs 22.3

21.8 vs 22.7

20.4 vs 17.8

27.8 vs 23.9

30.8 vs 20.6

19.4 vs 24.6

0.5 1.0 2.0

START: OS in Patients With

Concurrent Chemo/RT

L-BLP25 (n = 538)

Placebo (n = 268)

Median OS, mos 30.8 20.6

HR 0.78 (95% CI: 0.65-0.95; P = .016*)

227

499

118

295

Placebo

L-BLP25

268

538

186

412

73

205

62

176

54

147

40

89

26

51

16

24

4

7

0

0

Pts at Risk, n

Su

rviv

al (%

)

*2-sided, adjusted for strata

Mos

L-BLP25

Placebo

100

90

80

70

60

50

40

30

20

10

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


START: Safety

AE, % Tecemotide (n = 1024)

Placebo (n = 477)

Most frequent AEs (> 10% in tecemotide arm)

Cough 33.0 27.9

Dyspnea 23.2 23.5

Fatigue 19.2 21.4

Back pain 14.3 11.1

Nausea 13.7 8.2

Chest pain 13.2 9.4

Nasopharyngitis 12.5 9.2

Headache 12.1 11.3

Decreased appetite 10.6 9.2

Arthralgia 10.5 7.1

Influenzalike symptoms

• Any 38.2 33.1

• Grade 3/4 1.5 1.7

Pa

tie

nts

(%

)


100

90

80

70

60

50

40

30

20

10

0

91.6 90.6

33.4 35.8

29.6 31.7

4.5 7.3

Any AE Any

Grade

3/4 AE

Any

Serious

AE

Any AE

Leading

to Death

Tecemotide (n = 1024)

Placebo (n = 477)

Summary

• Study did not meet primary endpoint of significant improvement in OS with use of tecemotide maintenance

• Prespecified subgroup analysis identified significant 10.2-mo OS benefit with tecemotide in patients who received concurrent initial chemotherapy and radiotherapy

• Tecemotide therapy was well tolerated

– AE incidence similar to placebo

#2658: Interim analysis of the Spanish Lung Cancer Group (SLCG) randomized phase II trial of thoracic radiotherapy (RT) concurrent with cisplatin (P) plus oral vinorelbine (OV) or etoposide (E) for unresectable locally advanced (LA) stage III non-small cell lung cancer (NSCLC). (GECP10/02).

Dolores Isla1, Ramon De Las Penas, Natividad Martinez-Banaclocha, Bartomeu Massuti, Maria Angeles Sala, Isabel Bover, Raquel Marse, Amelia Insa, Teresa Moran, Angel Artal, Pilar Diz, Jose Gomez-Codina, Ana Laura Ortega, Vanesa

Gutierrez, Jose Munoz, Melchor Alvarez De Mon, Carlos Camps, Ramon Garcia-Gomez, Jose M. Jurado, Santiago Ponce-Aix, Mariano Provencio

# 2658: Interim analysis of the Spanish Lung Cancer Group (SLCG) randomized phase II trial of thoracic radiotherapy (RT) concurrent with cisplatin (P) plus oral vinorelbine (OV) or etoposide (E) for unresectable locally advanced (LA) stage III non-small cell lung cancer (NSCLC). (GECP10/02). Dolores Isla

STUDY DESIGN

Multicentric randomized phase II trial Patients with non-resectable stage IIIA – IIIB NSCLC PS ECOG 0-1, Age ≤ 75 years, Weight loss < 5% / 3 m., Adequate lung function

Arm A: 2 cycles Induction CT: Vinorelbine Oral 80 mg/m2 (1st cycle 60 mg/m2) D1 D8 CDDP 80 mg/m2 D1 Every 3 weeks

2 cycles Concomitant CT-RT: Vinorelbine Oral 40 mg/m2 D1 D8 CDDP 80 mg/m2 D1

RT 66 Gy Every 3 weeks

Arm B: 2 cycles Concomitant CT-RT: Etoposide 50 mg/m2 D1 to D5

CDDP 50 mg/m2 D1 D8

RT 66 Gy Every 4 weeks

Thoracic RT: Standard 3D conformal RT by linear accelerator with >6 MV rays, Total dose: 66 Gy / 33 daily fractions / 2 Gy (5 dy/w)

Total sample size: 67 patients per arm Accrual start date: August 2011

CHARACTERISTIC ARM A

OVNR + CDDP N=34

ARM B

E + CDDP N=34

Median age, yr (range) 64 (45-75) 60 (43-71)

Gender, %: Male

Female

91.2

8,8

88.2

11.8

ECOG PS, %: 0

1

58.8

41.2

32.4

67.6

Smokers, %: Current

Never

Former

47.1

2.9

50

50

0

50

Histology, %:Squamous

Adenocarcinoma

Large cell

55.9

41.2

2.9

52.9

44.1

2.9

Stage, %: IIIA

IIIB

IV*

52.9

44.1

2.9

47.1

52.9

0


N of Participating Sites: 25 N of Patients Analized: 68 (total of 134)

PATIENT CHARACTERISTICS

* 1 inclusion failure, who did not receive study treatment but included in the ITT analysis.

RESPONSE * ARM A

OVNR + CDDP N=22

ARM B E + CDDP

N=24

CR 4.5 % 4.2 %

PR 63.7 % 50 %

OR (CR + PR) 68.2 % 54.2 %

SD 22.7 % 29.1 %

PD 9.1 % 16.7 %

RESPONSE RATE


* Evaluable population

HEMATOLOGICAL

TOXICITIES % of cycles

ARM A OVNR + CDDP

N = 98 cy

ARM B

E + CDDP

N = 56 cy

Anemia 0 3.57

Neutropenia 6.12 12.50

Febrile neutropenia 3.06 1.79

Leucopenia 2.04 8.93

Thrombocytopenia 0 5.36

NON-

HEMATOLOGICAL

TOXICITIES % of cycles

ARM A OVNR +

CDDP

N = 98 cy

ARM B E + CDDP

N = 56 cy

Asthenia/fatigue 1.02 1.79

Diarrhoea 1.02 0

Esophagitis 0 8.93

Infection 1.02 7.14

Mucositis 1.02 1.79

Alopecia (grades 1/2) 6.12 37.5


TOXICITY Grade ¾

Safety Data from a Phase II Study of Pemetrexed (PEM) and Cisplatin (CIS) with Concurrent Thoracic Radiation after PEM+CIS Induction in

Patients with Unresectable Locally Advanced (LA) Non-Squamous Non-Small Cell Lung Cancer (NS-NSCLC)

P. Garrido1, M. Serke2, S. Novello3, P. Giraud4, C. Visseren-Grul5, S. Ameryckx6, V. Soldatenkova7,

N. Chouaki8, W. Engel-Riedel9

1University Hospital Ramon Y Cajal, Madrid, Spain; 2Hemer Lung Clinic, Hemer, Germany; 3S. Luigi Hospital, University of Turin, Orbassano, Italy; 4Georges Pompidou European Hospital, Paris, France; 5Medical Oncology, Eli Lilly and Company, Houten, The

Netherlands; 6Global Clinical Trial Management, Lilly S.A. Eli Lilly Benelux N.V., Brussels, Belgium; 7European Statistics, Oncology, Lilly Deutschland GmbH, Bad Homburg, Germany; 8Medical Oncology, Lilly France, Neuilly sur Seine, France; 9Lung Clinic Merheim, Hospital

of Cologne, Cologne, Germany

Background

• Concurrent chemo- and radiotherapy (CT+RT) is standard of care for most patients with locally advanced unresectable NSCLC, but no specific CT regimen is recommended1,2

• PEM synergizes with ionizing radiation and CIS in preclinical models3,4

• PEM+CIS doublets showed efficacy and favourable toxicity profiles in Phase I/II studies of locally advanced NSCLC when combined with thoracic RT5,6

• Concurrent CT+RT preceded by induction has been tested in Phase III, using a CARBO-based regimen1,7

1Vansteenkiste et al., Ann Oncol 2013 [epub]; 2Auperin et al., J Clin Oncol 2010;28:2181-90; 3Wagner and Yang, Curr Drug Targets 2010;11:67-73 4 Bischof et al., Int J Radiat Oncol Biol Phys 2002;52:1381-88 5 Brade et al., Int J Radiat Oncol Biol Phys 2011;79:1395-401 6 Gadgeel et al., J Thorac Oncol 2011;6:927-33 7 Vokes et al., J Clin Oncol 2007;25:1698-704

Objectives

• Primary objective: To assess the antitumor activity of PEM+CIS as induction, followed by PEM+CIS with concurrent thoracic RT, as measured by 1-year progression-free survival (PFS) rate

• Secondary objectives:

– Objective tumor response rate (RR)

– Overall survival (OS)

– Safety and tolerability

Study Design

1American Joint Committee on Cancer TNM Staging System for Lung Cancer, 6th edition, 2002

2Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.0; Therasse et al., J Natl Cancer Inst 2000;92:205-16.

All patients received folic acid, vitamin B12 and dexamethasone as per PEM label

Treatment Period

Induction CT (2 cycles) Concurrent CT (2 cycles) + RT

500 mg/m2 pemetrexed +

75 mg/m2 cisplatin, d1, q21d

Concurrent CT + RT started if:

• CR, PR, SD

• ECOG PS 0/1

Patients enrolled if:

• Non-squamous NSCLC

• Stage IIIA/IIIB (AJCC Version 6)1

• ECOG PS 0/1

500 mg/m2 pemetrexed +

75 mg/m2 cisplatin, d1, q21d

3D conformal RT:

Total dose 66 Gy

33 fractions of 2 Gy

FU

≥ 2 years

follow-up

2

Summary of CT and RT Exposure

Cycles received, n (%) All patients (N = 90)

Completed 2 cycles of induction CT 85 (94.4)

Started concurrent CT+RT 75 (83.3)

Completed 4 cycles of CT 72 (80.0)a

a 64/72 patients also received ≥60 Gy of RT („completed treatment“)

RT dose received, n (%) All patients (N = 90)

Started concurrent CT+RT 75 (83.3)

Received full dose (66 Gy) 65 (72.2)

Received 60 to <66 Gy 4 (4.4)

Received <60 Gyb 6 (6.7)

b Range 18 – 52 Gy/9 – 26 fractions

Time (months)

0 6 12 18 24 30

PF

S P

rob

ab

ilit

y

0.0

0.2

0.4

0.6

0.8

1.0

Progression free survival

Proximity of Disease Progression to Radiation Field

All patients (N = 90) n (%)

With documented disease progression 53 (58.9)

With PD and not eligible to receive RT 12 (13.3)

Documented PD and started CT+RT 41 (45.6)

Local disease progression 19 (21.1)

Within radiation field 14 (15.6)

Outside of radiation field, within thorax 5 (5.6)

Distant metastases 22 (24.4)

Tumor Response (RECIST 1.0)

All patients (N = 90)

Best overall response n (%)

Complete response (CR) 7 (7.8)a

Partial response (PR) 46 (51.1)

Response rate (CR+PR) 53 (58.9) 95% CI: 48.0, 69.2

Stable disease (SD) 17 (18.9)

Disease control rate (CR+PR+SD) 70 (77.8) 95% CI: 67.8, 85.9

Progressive disease (PD) 12 (13.3)

Not evaluableb/not done 7b/1 (7.8/1.1)

a 3 patients after CT+RT, 4 patients after CT+RT + surgery b 7 patients who discontinued study treatment before starting the concurrent CT+RT phase due to reasons other than

PD were considered as not evaluable for best overall response.

RECIST 1.0: Therasse et al., J Natl Cancer Inst 2000;92:205-16

Safety Data – Overview

All patients (N = 90) n (%) with event

Any treatment-emergent adverse event (TEAE) 85 (94.4)

Grade 3/4 TEAEs 38 (42.2)

Related to study treatment 33 (36.7)

Serious TEAEs 23 (25.6)

Related to study treatment 17 (18.9)

Death due to toxicity 1 (1.1)a

Adverse events leading to discontinuation 6 (6.7)

Related to study treatment 4 (4.4)b

a Death due to enteritis, during concurrent CT+RT, Cycle 4 b 1 patient had renal failure, 1 patient had hypoacusis, 2 patients had radiation esophagitis

Analysis of adverse events according to NCI-CTCAE, Version 3.0 .

Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf

Grade 3/4 Toxicities (CTCAE)

Number (%) of patients with G3/4 CTCAEs

During Induction CT

N = 90

During conc. CT+RT N = 75

During complete treatment period

N = 90

Hematologic

Neutropenia 2 (2.2) 8 (10.7) 8 (8.9)

Leukopenia 0 7 (9.3) 7 (7.8)

Thrombocytopenia 0 2 (2.7) 2 (2.2)

Anemia 0 1 (1.3) 1 (1.1)

Non-hematologic toxicities a,b

Esophagitis/dysphagia 0 9 (12.0) 9 (10.0)

Mucositis 0 1 (1.3) 1 (1.1)

Acute pneumonitis 1 (1.1) 1 (1.3) 2 (2.2)

a Selected based on clinical relevance for combined CT+RT b Only 1 G4 esophagitis, all other events reported in Table were G3

Conclusions

In this study of PEM+CIS induction, followed by concurrent full-dose PEM+CIS plus RT in patients with locally advanced NS-NSCLC:

• PFS (1-year rate 51.3%) was in the same range as previously observed with other CIS-based induction CT followed by concurrent CT+RT1,2

• The overall response rate was 58.9% (disease control rate 77.8%)

• Delivery of full dose PEM+CIS CT+RT was feasible, with 71% of patients completing treatment

• Grade 3/4 toxicities ≥10% during concurrent CT+RT included esophagitis (12%) and neutropenia (11%), which are considered acceptable for locally advanced NSCLC

1 Descourt et al., J Thorac Oncol 2011;6:351-57 2Fournel et al., J Clin Oncol 2006; 24(June 20 Suppl):7048

Comentarios a futuro: ¿Denver 2015?

• Es necesario realizar estudios en subgrupos específicos de los estadios IIIA-IIIB

• Son necesarios factores predictivos de individualización terapéutica

• Son necesarios estudios en las poblaciones mayoritarias (comorbilidad, edad)

• Es necesario incluir en objetivos de los estudios toxicidad y valoración subjetiva

Albert Camus (1913-1960)

• Adquirimos la costumbre de vivir antes que la de pensar". (El mito de Sísifo).

• “Lo que más distingue al hombre del animal es la imaginación”. (Carnets 2)

A. Camus Obras Completas Alianza Editorial. Madrid 1996

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09 Tratamiento combinado de quimio y radioterapia en Cáncer de Pulmón

Health & Medicine

Transcript of 09 Tratamiento combinado de quimio y radioterapia en Cáncer de Pulmón