CANCER PULMON: ESTADIOS INICIALES

POSTMUNDIAL PULMON DENVER 2015

8-10-2015.Manuel Cobo DolsS. Oncología Médica HU Málaga Regional y VV

Meta-analisis LACE: adyuvancia vs no adyuvancia

Pignon JP, et al . JCO 2008

Lancet 2014

Meta-analisis adyuvancia Pulmón. Pignon JP, et al . JCO 2008

Strauss GM. CALGB adyuvante. JCO 2008

SG > 4 cm SG < 4 cm

Estadio IB. Adyuvancian Analisis a largo plazo ANITA: No beneficio estadio I

n CALGB 9333.Analisis SG a 9 años (Strauss ASCO 2011)

n< 4 cm HR 0.92, p = 0.363

n> 4 cm HR 0.78, p =0.087

n JBR-10. Subanálisis estadio I

n> 4 cm, HR 0.66, p=1.14

n< 4 cm, HR 1.73. p = 0.06.

n El tamaño tumoral es un factor relevante en el antiguo

Estadio I, pero no se ha validado prospectivamente

Estadiaje: Intención, enfoque tratamiento

vc

Conclusiones estadios precocesn Estándar: Cirugía completa.

n Si no se puede cirugía completa: SBRT

n Quimioterapia adyuvante: 4 ciclos CDDP- NVB

nNO en estadios IA (< 3 cm).

nSI en IIB: T3 ( >7 cm u otros criterios T3)

nSI en N +

nSI /? en IIA: T2b ( 5-7 cm).

nSI / NO en IB : T2a ( 4-5 cm). Casos seleccionados

nNO en PS 2-3.

nSI en > 70 sin comorbilidades importantes

ORAL04.01: Final Results of Phase III Trial of Adjuvant Chemo-Immunotherapy in Lung Cancer – Kimura H et al

• Key results– Subgroup analysis identified those who were male, had adenocarcinoma, were stage III or

had no preoperative chemotherapy to have poorer prognosis with lower HRs

– CD8/CD4 ratio was significantly elevated in survivors

• Conclusions– The use immunotherapy in adjuvant treatment of patients with NSCLC was shown to

improve survival

– A large-scale multi-institutional trial is required to validate these findings

Kimura et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL04.01

Chemo-immunotherapy Chemotherapy

2-year OS, % 96.0 64.7

5-year OS, % 74.6 40.9

OS, HR (95%CI); p-value 0.321 (1.64, 0.631); p=0.001

2-year RFS, % 68.0 41.2

5-year RFS, % 57.2 29.2

RFS, HR (95%CI); p-value 0.435 (0.253, 0.749); p=0.0027

Study of Pembrolizumab (MK-3475) vs Placebo for Participants With Non-small Cell Lung Cancer After Resection With or Without Standard Adjuvant Therapy (MK-3475-091/KEYNOTE-091) (PEARLS)

RANDOMIZE

Pembolizumab 200 mg, intravenously (IV), every 3

weeks, for one year (expected maximum 18 doses).

Placebo

N= 1380

Main endpoint: PFS

•IB with T ≥ 4 cm, II-IIIA •4 cycles of adjuvant CT•Completely resected disease •Available tumor sample obtained at surgical resection for PD-L1 Immunohistochemistry (IHC) expression assessment

JTO 2015, abstrct 2219

RT adyuvante en N2 resecados

Lally B E et al. JCO 2006;24:2998-3006

Base datos SEER

Phase III Study Comparing Post-Operative Conformal Radiotherapy to No Post-Operative Radiotherapy in Patients With Completely Resected Non-Small Cell Lung Cancer and Mediastinal N2

Involvement [Lung ART]

RANDOMIZE

PORT post-operative

observation

Clinical stage

IIIA= N2 postCX

N=700

Main endpoint: PFS

•N2 mediastinal nodal involvement prior to neoadjuvant chemotherapy OR at the time of surgery in the absence of neoadjuvant chemotherapy •Completely resected disease by lobectomy, bilobectomy, or pneumonectomy (absence of positive margins or extracapsular extension in a node removed separately)•Mediastinal lymph node exploration (lymph node sampling or systematic dissection of lymph nodes at stations 2, 4 and 7 in case of upper/middle right-sided lung cancer; 4, 7, 8 and 9 in case of lower right-sided lung cancer; 5, 6 and 7 in case of upper left -sided lung cancer; 7, 8 and 9 in case of lower left-sided lung cancer is recommended)

ORAL05.02: Quality of Resection in Pathological N2 NSCLC in the Phase 3 Lung Adjuvant Radiotherapy Trial (Lung ART): An Important Factor – Edwards J et al

Study objective• To explore the impact of post-operative conformal radiotherapy on disease-free survival in

patients with completely resected pathologically proven N2 NSCLC with/without induction or adjuvant chemotherapy

Edwards et al. J Thorac Oncol 2015; 10 (suppl 2): ORAL05.02

Key patient inclusion criteria

• Completely resected NSCLC

• Histologically or cytologicallyproven N2 nodal involvement

• No metastasis

• No previous RT

• Age >18 years

• WHO PS ≤1

(n=116)

Post-operative conformal RT (54 Gy)

PD

Primary endpoint

• DFS

Stratification factors• Institution, adjuvant chemotherapy, histology,

mediastinal lymph node involvement, pretreatment PET-scan

R

PDControl

Nodal evaluation n (%)

Sampling 18 (16)

Selective dissection 26 (22)

Systematic dissection 72 (62)

• Key results

– Nodal dissection was performed in 71% of the patients as per the recommendations

– More than 80% of patients had >2 mediastinal stations explored; station 7 was explored in 106/116 (91%)