combined modality treatment for n2 disease · combined modality treatment for n2 disease dr clara...
TRANSCRIPT
![Page 1: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/1.jpg)
The Christie NHS Foundation Trust
Combined modality treatment for N2 disease
Dr Clara Chan
Consultant in Clinical Oncology
8th March 2019
![Page 2: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/2.jpg)
The Christie NHS Foundation Trust
DISCLOSURE OF INTEREST
No disclosures.
![Page 3: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/3.jpg)
The Christie NHS Foundation Trust
Overview
• Background
• The evidence base
• Systemic treatment
• Radiotherapy
• Future directions/clinical trials
![Page 4: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/4.jpg)
The Christie NHS Foundation Trust
Background
• 25-30% of NSCLC pts have stage III disease
• Few locally advanced NSCLC patients are candidates
for surgery
• Survival is poor
• stage IIIA 10-25% 5 year survival
• Scope for improving local and distant control
![Page 5: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/5.jpg)
The Christie NHS Foundation Trust
![Page 6: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/6.jpg)
The Christie NHS Foundation Trust
Radical treatment options for N2 disease
• Surgery
• Radiotherapy alone
• Sequential chemo-radiotherapy
• Concurrent chemo-radiotherapy
• Trimodality treatment
![Page 7: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/7.jpg)
The Christie NHS Foundation Trust
Radical treatment options for N2 disease
• Surgery
• Radiotherapy alone
• Sequential chemo-radiotherapy
• Concurrent chemo-radiotherapy
• Trimodality treatment
![Page 8: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/8.jpg)
The Christie NHS Foundation Trust
Sequential chemoradiotherapy
• BMJ metanalysis 1995:
• hazard ratio of 0.87 in favour of combined treatment
• 13% reduction in the risk of death
• Absolute benefit of 4% at two years
• Heterogeneity in chemotherapy regimens and
radiotherapy schedules used
![Page 9: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/9.jpg)
The Christie NHS Foundation Trust
Concurrent chemoradiotherapy
• Auperin metanalysis
2010: • Concurrent CTRT
superior to sequential
• HR 0.83 overall survival
in favour of concurrent
• 4.5% survival benefit at
5 years
• Significantly higher
oesophagitis rate (HR
4.9)
• similar pneumonitis rate
Anne Aupérin et al. JCO 2010;28:2181-2190
![Page 10: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/10.jpg)
The Christie NHS Foundation Trust
Walter J. Curran, Jr et al. JNCI J Natl Cancer Inst 2011;103:1452-1460
Concurrent chemoradiotherapy
• RTOG 9410
• Concurrent CTRT
superior to sequential
• 5 yr survival 16% v
10% (p=0.046)
• Acute G3-5 toxicity
higher with concurrent
• Late toxic effects
similar
![Page 11: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/11.jpg)
The Christie NHS Foundation Trust
Patient selection
• Performance status
PS 0-1
• Co morbidities
• PET
Encompassable within radical field
• Mediastinal staging
• Brain imaging
• Pulmonary function testing
• FEV1 > 40%
• KCO >40%
• Age
![Page 12: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/12.jpg)
The Christie NHS Foundation Trust
Which chemotherapy?
• Platinum based chemo with 3rd generation drugs
• Taxol/Gemcitabine/Vinorelbine (reduced doses)
• Cisplatin/Etoposide (full dose)
• Emerging role for Carboplatin/Paclitaxel
• No benefit of Pemetrexed in concurrent setting (PROCLAIM trial)
• No evidence to support the use of TKI in the
concurrent setting
Vokes JCO 2002, Hanna JCO 2008, Santana-Devilla JCO 2015
Senan, JCO 2016
![Page 13: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/13.jpg)
The Christie NHS Foundation Trust
? More systemic treatment
• Concurrent CTRT optimises local control but
distant spread is still a major problem
• Further systemic treatment to optimise treatment
of distant disease
![Page 14: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/14.jpg)
The Christie NHS Foundation Trust
? More systemic treatment
• No benefit to induction chemotherapy
• CALGB 39801 (Vokes, JCO 2007)
• No benefit to consolidation chemotherapy
• HOG 01-24 (Hanna, JCO 2008)
• KCSG-LU05-04 (Ahn, JCO 2015)
![Page 15: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/15.jpg)
Consolidation Immunotherapy -PACIFIC
• Unresectable, Stage III NSCLC
without progression after definitive
platinum-based cCRT (≥2 cycles)
• 18 years or older
• WHO PS score 0 or 1
• If available, archived pre-cCRT
tumor tissue for PD-L1 testing*
All-comers population
(i.e. irrespective of PD-L1 status)
N=713 randomized
Durvalumab10 mg/kg q2w for
up to 12 months
N=476
Placebo
for up to 12 months
N=237
2:1 randomization,
stratified by age, sex,
and smoking history
R
1–42 days
post-cCRT
Antonia S, et al. NEJM 2017; 377:1919–29;
Antonia S, et al. NEJM 2018; 379:2342-2350
![Page 16: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/16.jpg)
PFS HR = 0.52 95% CI, 0.42–0.65
P<0.001
Antonia S, et al. NEJM 2017; 377:1919–29
![Page 17: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/17.jpg)
OS HR = 0.68 99.73% CI, 0.469–0.997†
P=0.00251
Antonia S, et al. NEJM 2018; 379:2342-2350
![Page 18: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/18.jpg)
The Christie NHS Foundation Trust
Radiotherapy planning
• RT commences D1 chemotherapy
• RT planning scan done asap
• Motion management
• 4D CT
• Respiratory gating/Breath hold
• Advanced RT techniques
• IMRT
• IGRT
![Page 19: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/19.jpg)
The Christie NHS Foundation Trust
4D CT
![Page 20: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/20.jpg)
The Christie NHS Foundation Trust
Intensity Modulated RadiotherapyIMRT
• Improved conformity
• Avoidance of radiosensitive structures eg spinal cord
• Retreatments
• Large volumes
![Page 21: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/21.jpg)
The Christie NHS Foundation Trust
• Sequential CTRT
• 60-66Gy/30-33# OD
• 55Gy/20# OD
• 54Gy/36# TDS (CHART)
• Concurrent CTRT
• 60-66 Gy in 30-33 fractions OD
What RT?
![Page 22: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/22.jpg)
The Christie NHS Foundation Trust
More radiotherapy?
• Greater local control correlates with improved
survival
• Modern RT techniques allow dose escalation
• Recent RTOG 0617 study
• No defined role for dose escalation
![Page 23: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/23.jpg)
The Christie NHS Foundation Trust
RTOG 0617
• Higher dose arm:
• Greater risk of locoregional failure
• Poorer survival
Lo
ca
l P
rog
ressio
n R
ate
(%
)
0
25
50
75
100
Months since Randomization
0 3 6 9 12 15 18
Patients at RiskStandardHigh dose
213206
205197
187170
165134
137105
113 80
85 62
Fail
6581
HR=1.37 (0.99, 1.89)
Total
213206
p=0.0319
Standard (60 Gy)High dose (74 Gy)
Su
rviv
al R
ate
(%
)
0
25
50
75
100
Months since Randomization
0 3 6 9 12 15 18
Patients at RiskStandardHigh dose
213206
207197
190178
177159
161135
141112
108 87
Dead
90117
Total
213206
HR=1.56 (1.19, 2.06) p=0.0007
Standard (60 Gy)High dose (74 Gy)
![Page 24: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/24.jpg)
The Christie NHS Foundation Trust
Chemoradiotherapy – summary
• Gold standard: Concurrent platinum based CTRT
• No consensus on chemo regimen
• Modern RT techniques allow better sparing of normal
tissue
• For patients with > 1% PD-L1 expression,
maintenance Durvalumab now standard of care
• For patients unsuitable for concurrent treatment,
sequential CTRT or radiotherapy alone
• No benefit to radiotherapy dose escalation with
conventional fractionation
![Page 25: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/25.jpg)
The Christie NHS Foundation Trust
What combination of treatment is best for potentially resectable N2
disease?
![Page 26: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/26.jpg)
The Christie NHS Foundation Trust
EORTC 08941 – overall survival
Van Meerberck et al, J Natl Cancer Inst 2007;99:442-50
![Page 27: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/27.jpg)
The Christie NHS Foundation TrustAlbain, Lancet. 2009 Aug 1;374(9687):379-86
![Page 28: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/28.jpg)
The Christie NHS Foundation Trust
SAKK 16/00
Pless et al, Lancet 2015
![Page 29: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/29.jpg)
The Christie NHS Foundation Trust
Potentially resectable N2 disease –summary
• Trimodality treatment may have a role in selected
operable cases
• No survival benefit to surgery over definitive CTRT
• Uncertain benefit of induction CTRT versus chemotherapy
• Importance of
• Team working/MDT decision
• Local surgical expertise (avoid pneumonectomies)
![Page 30: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/30.jpg)
The Christie NHS Foundation Trust
Have we made progress in inoperable stage III NSCLC?
CAUTION! Will Rodger phenomenon
Median survival(months)
2 yrssurvival
RT 10 15%
CT → RT 14 30%
CTRT
prePET erapostPET era
1724-26
35%Up to 60%
![Page 31: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/31.jpg)
The Christie NHS Foundation Trust
Future directions
• Individualised treatment
• Personalised RT dose
• Combinations with novel agents
• Proton therapy
![Page 32: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/32.jpg)
The Christie NHS Foundation Trust
ADSCaNA Randomised Phase II study of Accelerated, Dose escalated, Sequential
Chemo-radiotherapy in Non-Small Cell Lung Cancer
![Page 33: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/33.jpg)
The Christie NHS Foundation Trust
CONCORDEPlatform study of novel agents in COmbinatioN with
COnventional RaDiothErapy in locally advanced disease
![Page 34: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/34.jpg)
The Christie NHS Foundation Trust
PACIFIC-2
A phase III placebo controlled study of Durvalumab + RCTfollowed by Durvalumab maintenance for unresectable stage III NSCLC
R
PD
PDKey patient inclusion criteria
• Unresectable stage III NSCLC
• ECOG 0-1
• No progression after
chemoradiotherapy (≥2 cycles of
platinum based and ≥50 Gy)
(n=300)CRT 60Gy + Placebo
---Placebo maintenance
CRT 60Gy + Durvalumab
--- Durvalumab maintenance
Primary endpoint
PFS, ORRNCT03519971
![Page 35: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/35.jpg)
The Christie NHS Foundation Trust
Take home messages
• Concurrent platinum based chemoradiotherapy remains
gold standard for inoperable N2 disease
• Overall survival benefit to consolidation Durvalumab
• No benefit to radiotherapy dose escalation
• Trimodality treatment may be appropriate in selected
operable cases
• Improved RT techniques may allow greater
individualisation of treatment in the future
![Page 36: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/36.jpg)
The Christie NHS Foundation Trust
![Page 37: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/37.jpg)
The Christie NHS Foundation Trust
Consolidation Pembrolizumab Following CCRT for Unresectable Stage III NSCLC: LUN 14-179
Presented By Greg Durm at 2018 ASCO Annual Meeting
N=92
![Page 38: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/38.jpg)
The ETOP NICOLAS phase II trial with Nivolumab
� Interim safety analysis
Pneumonitis-free rate of grade≥3 at 3 months post-RT
Assumption: 70% of the events occur within the 3 months
n=21 (O’Brien-Fleming approach)
Success Rule: NO events
Hierarchical design: IF safety proven ����
• Key-secondary efficacy evaluation: 1-year PFS
Hs0: PFS0≤45% vs Hs1: PFS1>60%
n=74 (1-sided alpha=5%, power=83%).
Sequential administration of chemo-RT
was allowed before amendment for
efficacy
Slide courtesy of Prof. Solange PetersASCO 2018 - ETOP NICOLAS trial
![Page 39: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/39.jpg)
The Christie NHS Foundation TrustNCT03102242
Concurrent chemoradiation
60Gy/30fx+ Carbo/paclitaxel weekly
Consolidation
Carbo/paclitaxel x
2
+ Adjuvant ATEZO
for 1 year
Unresectable Stage IIIA/IIIB
ATEZO 1200mg q 3 weeks x 4
Restaging post 2 and 4 cycles
Primary endpoint: Disease control rate at week 12
N=63
ALLIANCE Phase II Induction/Adjuvant Atezolizumab
![Page 40: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/40.jpg)
The Christie NHS Foundation Trust
1:1
Concurrent chemoradiationstage III NSCLC
RT dose: 59.4-66.6 Gy
Cisplatin/Etoposide,
Carboplatin/Paclitaxel or
Cisplatin/Pemetrexed
Consolidation chemo allowed (x2)
PET scan post treatment
mandatoryNIVO 3mg/kg x12 q 2 weeks
+ IPI 1 mg/kg x 4 q 6 weeks
NIVO 480mg q 4 weeks x 6
NCT03285321
N=108Primary endpoint: PFSSecondary endpoints: OS, TTDM, Safety
BTCRC LUN16 - 081
![Page 41: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/41.jpg)
The Christie NHS Foundation Trust
T2-4 N0-3 M0
Primary tumor
diameter > 4 cm
SUVmax > 5.0
Eligible for
radical treatment
(RT only, seq or conc)
RegisterDose
Planning
Start dose
66 Gy
in 24 fractions
<72 Gy Dose
escalation
not possible
> 72 Gy Dose
escalation
possible
RANDOMISED
radiotherapy
to tolerance
RT
Homogeneous
Boost
(Arm A)
RT
inhomogeneous
Boost 50% SUVmax
(Arm B)
Proceed with treatment plan for Arm A
(boost entire primary tumour)
-If primary tumour dose < 72 Gy
=> patient treated up to this dose level (no
randomization)
- If primary tumour dose ≥ 72 Gy
⇒ patient is randomized between Arm A and Arm B
Primary endpoint: LPFS at 1 year
PET boost- ARTFORCE
MLD 20 GyMed envelope and heart 76 GyBrachial Plexus 79 GySpinal Cord 53 Gy Oesophagus: V36 < 80%.
![Page 42: Combined modality treatment for N2 disease · Combined modality treatment for N2 disease Dr Clara Chan Consultant in Clinical Oncology ... Chemo-radiotherapy in Non-Small Cell Lung](https://reader036.vdocuments.us/reader036/viewer/2022071403/60f7a7f6af054d16ce254d9d/html5/thumbnails/42.jpg)
The Christie NHS Foundation Trust
RTOG-EORTC randomised phase II study in stage III NSCLC with
EGFR TK mutations or EML4- ALK fusion gene
†Per treating physician’s discretion, a choice of the following chemotherapy regimens:
Cisplatin and etoposide every 4 weeks for 2 cycles
Paclitaxel and carboplatin weekly for 6 weeks followed by 2 cycles of consolidation
Pemetrexed 500 mg/m2 and carboplatin AUC-5 every 3 weeks for a maximum of 4 cycles
Patients with EGFR TK or EML4-ALK fusion arrangement (done at a CLIA certified lab) will be enrolled
† Concurrent chemotherapy
and radiation 64 Gy
Ra
nd
om
ise
Crizotinib 250mg/bid for 12 weeks
Ra
nd
om
ise
† Concurrent chemotherapy
and radiation 64 Gy
† Concurrent chemotherapy
and radiation 64 Gy
† Concurrent chemotherapy
and radiation 64 Gy
Eriotinib 150mg/day for 12 weeks
EGFR +
ALK +
Weight loss ≤5%
Weight loss >5%
EGFR +
Weight loss ≤5%