What to do in stage III non
small-cell lung cancer?
Miklos Pless
28. November 2013
CRT: Concomitant vs. Sequential
Meta-Analysis 2010 (HR 0.84, Cochrane 0.74)
Auperin, JCO 2010
2
CRT: Chemotherapy type not so important?
CALGB 9431 (phase II)
Vokes, JCO 2007
3
CRT: Role of induction chemotherapy
CALGB 39801
Vokes, JCO 2007
4
CRT: role of consolidation CT after CRT?
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
Yamamoto S. et al., J. Clin. Oncol. 30, 2012, suppl. Abstr.7000
5
CRT: role of hyperfractionation
RTOG 9410
Arm 3: 70 Gy: 1.2 Gy 2x/d
Arm 2: 63 Gy: 1.8 Gy/d
HR 0.925
Curran, JNCI 2011
6
CRT: Role of high doses of RT
RTOG 0617
7
Bradley , ASCO 2013
Operable stage IIIA:
Adjuvant Chemotherapy: OS better!
Winton, NEJM 2005
8
Operable Stage IIIA
Does adjuvant RT help? NO!
PORT Cochrane, 2010
9
JNCI, 2007
•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
10
Lancet 2009
 Resectable N2
 Induction CRT:
3x Cis/Eto + RT 45 Gy
 If no PD:
RT to 61Gy vs. OP
 1. EP: OS
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OS
PFS
The activity of the SAKK group
SAKK 16/96 (Phase II)
3 x Cisplatin/Taxotere neoadjuvant (Betticher, JCO 2003)
Overall Survival (ITT population, n=90)
Overall survival
1
complete
.8
resection
.6
all
.4
.2
incomplete
p<0.0001
0
resection
0
12
10
20
30
40
50
60
Months
Is trimodal better than bimodal?
SAKK 16/00
Stratification factors: Mediastinal bulk (≥5cm vs. <5cm), weight loss (≥5% vs. <5% in
past 6 months), center
Arm A: RT
Chemotherapy
*
3-4 weeks
Radiotherapy
*
Surgery
44 Gy in 22 fractions in 3
weeks
CDDP 100mg/m2 d1 x 3 cy q3w Accelerated conc. boost
DXT
Arm B: no RT
Randomization
3 weeks
85mg/m2 d1 x 3 cy q3w
+G-CSF
Chemotherapy
3-4 weeks
*
Surgery
* Staging: (PET-) CT: PD went off study
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Presented by: Miklos Pless
Overall Survival
1
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0.8
Overall Survival
Treatment
RT
no RT
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0.6
Median OS (95% CI)
27.1 (18.8, 42.8)
26.2 (21.0, 52.1)
HR = 1.145 (95% CI: 0.786-1669)
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0.4
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0.2
/
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Chemo/RT/Surgery
Chemo/Surgery
0
0
# at risk
RT
98
no RT 97
14
24
48
72
96
120
144
6
2
1
0
0
0
Time (months)
43
41
Pless ASCO 2013
19
21
7
10
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?
15
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
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