What to do in stage III non small-cell lung cancer?

Miklos Pless

28. November 2013

2

CRT: Concomitant vs. SequentialMeta-Analysis 2010 (HR 0.84, Cochrane 0.74)

Auperin, JCO 2010

3

CRT: Chemotherapy type not so important?CALGB 9431 (phase II)

Vokes, JCO 2007

4

Vokes, JCO 2007

CRT: Role of induction chemotherapyCALGB 39801

5Yamamoto S. et al., J. Clin. Oncol. 30, 2012, suppl. Abstr.7000

45 trials, 9 phase III, 36 phase II with 51 arms

No difference between the two groups,

med OS: CT 18.5 mo vs no CT 18.1 mo

CRT: role of consolidation CT after CRT?

6

HR 0.925

Curran, JNCI 2011

CRT: role of hyperfractionationRTOG 9410

Arm 3: 70 Gy: 1.2 Gy 2x/d

Arm 2: 63 Gy: 1.8 Gy/d

7

CRT: Role of high doses of RTRTOG 0617

Bradley , ASCO 2013

8

Operable stage IIIA:Adjuvant Chemotherapy: OS better!

Winton, NEJM 2005

9PORT Cochrane, 2010

Operable Stage IIIADoes adjuvant RT help? NO!

10

•Unresectable (?) N2

•With response to Induction

3 x Cis/Carbo + X

•OP vs. RT (60 Gy)

•1. EP: OS

•50% complete resection!

•41% downstaging to ≤ypN1

•Unresectable (?) N2

•With response to Induction

3 x Cis/Carbo + X

•OP vs. RT (60 Gy)

•1. EP: OS

•50% complete resection!

•41% downstaging to ≤ypN1

JNCI, 2007

11

Resectable N2 Induction CRT:

3x Cis/Eto + RT 45 Gy

If no PD: RT to 61Gy vs. OP

1. EP: OS

Resectable N2 Induction CRT:

3x Cis/Eto + RT 45 Gy

If no PD: RT to 61Gy vs. OP

1. EP: OS

Lancet 2009

PFSOS

12

The activity of the SAKK groupSAKK 16/96 (Phase II)

3 x Cisplatin/Taxotere neoadjuvant (Betticher, JCO 2003)Overall Survival (ITT population, n=90)

0

.2

.4

.6

.8

1

0 10 20 30 40 50 60

Months

Overall survival

complete

resection

incomplete

resectionp<0.0001

all

13

Is trimodal better than bimodal?SAKK 16/00

Presented by: Miklos Pless

Stratification factors: Mediastinal bulk (≥5cm vs. <5cm), weight loss (≥5% vs. <5% in past 6 months), center

*

* *

* Staging: (PET-) CT: PD went off study

14

Overall Survival

Treatment Median OS (95% CI)RT 27.1 (18.8, 42.8)

no RT 26.2 (21.0, 52.1)

HR = 1.145 (95% CI: 0.786-1669)

Pless ASCO 2013

Time (months)

Ove

rall

Su

rviv

al

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0 24 48 72 96 120 1440

0.2

0.4

0.6

0.8

1

# at riskRTno RT

98 43 19 7 6 1 097 41 21 10 2 0 0

Chemo/RT/SurgeryChemo/Surgery

15

Stage III

• Very heterogeneous disease

• <30% can be cured (70-80% are NOT!)

• Both local and distant relapse are a problem!

• Requires bimodal treatment

• always Chemotherapy: minor effect

• Surgery vs. Radiotherapy?

• Trimodal treatment?

16

Summary & Conclusions

Which Chemotherapy? (Cis-)Platinum based, concurrent

type and dose

Which Radiotherapy? >60 Gy, less than 70 Gy

type, dose, fraction

Which combination?

Surgery + Chemotherapy Stage IIIA/N2

Radiotherapy + Chemotherapy Stage IIIB/IIIA?

all three? Probably not