Early Stage Nsclc The Role Of Chemotherapy
-
Upload
fondas-vakalis -
Category
Health & Medicine
-
view
850 -
download
1
Transcript of Early Stage Nsclc The Role Of Chemotherapy
![Page 1: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/1.jpg)
Early Stage NSCLC: The Role of Chemotherapy
Eric Vallieres, MD
![Page 2: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/2.jpg)
Lung C ancerNSCLC 80%
SCLC 20%
> 60% / 5y
Stages IA / IBT1N0 / T2N0
10%17,20 0
30-50% / 5y
Stages IIA / IIBT1N1 / T2N1 & T3N0
20%34,40 0
10- 30 % / 5y
Stage IIIAT3N1, T1-3 N2
15%25,80 0
5% / 5 y
Stage IIIBT4, N3
15%25,80 0
Less than stage IV
<2% / 5y
Stage IVM1
40%68,80 0
Stage IV
172,000 new cases13 % / 5Y
![Page 3: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/3.jpg)
Clinical IB, IIA, IIB diseasesClinical IB, IIA, IIB diseases
• Resection by lobectomy or more if cardiopulmonary reserves
• 5-y Survival = 20-40 %
• Adjuvant Therapy ?• Induction Therapy ?
cT2N0 RUL NSCLC
![Page 4: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/4.jpg)
Adjuvant RadiotherapyAdjuvant Radiotherapy
![Page 5: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/5.jpg)
Adjuvant Radiotherapy
M RC Lung Cancer W orking Party
Observation Adjuvant RTx40 Gy / 15 fractions
T1-2 N1-2 NSCLCCom pletely resected (R0)
n = 308
N2 appeared to gain 1 month in survival...
![Page 6: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/6.jpg)
MRC LCWP
Stephens et al, Br J Cancer 1996
![Page 7: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/7.jpg)
Adjuvant RadiotherapyAdjuvant Radiotherapy
No improvement in survival
Improved loco-regional control with squamous histology (LCSG 773)
but
systemic failures lead to death...
![Page 8: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/8.jpg)
Adjuvant ChemotherapyAdjuvant Chemotherapy
![Page 9: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/9.jpg)
Adjuvant ChemotherapyAdjuvant Chemotherapy ALPI (Adjuvant Lung Project Italy) ALPI (Adjuvant Lung Project Italy)
O bserva tionn = 594
M V P *3n = 602
(C D D P 100 )
I ( .42 ), II ( .31 ), III ( .27 )NS C L C
R0 resec tions
Tonato, PASCO 2002 abstract 1157
![Page 10: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/10.jpg)
Overall SurvivalOverall Survival
Events/Total
CT 278/548
Control 288/540
HR=0.96 (0.81 - 1.13) p=0.585
PROBABILITY
YEARS
Median f/up of 63 months
![Page 11: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/11.jpg)
Adjuvant ChemotherapyAdjuvant Chemotherapy
Over the last 30 years, on trial, the delivery of the intended chemotherapy has been consistently
poor:
LCSG 801 (CAP * 4) = 53%
JCOG 8601 (C Vd *3) = 68%
ALPI (MVdP * 3) = 70%
![Page 12: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/12.jpg)
Clinical IB, IIA, IIB diseasesClinical IB, IIA, IIB diseases
• Resection by lobectomy or more if cardiopulmonary reserves
• 5-y Survival = 20-40 %
• Adjuvant Therapy = NO• Induction Therapy ?
cT2N0 RUL NSCLC
Scan not available
![Page 13: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/13.jpg)
3 cycles carboplatin/ paclitaxelre-imaged 4 weeks later
Pre Post
Scans not available
![Page 14: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/14.jpg)
Induction ChemotherapyThe BLOT Phase II StudyThe BLOT Phase II Study
Additional carbo/ paclitaxel * 3
Surgery
Carboplatin AUC 6Paclitaxel 225
2 cycles
Clinical Stages IB, IIA, IIB, T3N1Negative M ediastinoscopy
Pisters K et al., J Thor CV Surg 2000; 119:429-439
![Page 15: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/15.jpg)
The BLOT StudyThe BLOT Study
94 patients
98% completed induction chemo as planned
Clinical major RR: 53/90 ( 58.9%)
Pisters K et al., J Thor CV Surg 2000; 119;429
![Page 16: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/16.jpg)
The BLOT StudyThe BLOT Study
Progression during induction: 3/98 ( 3%)
Pisters K et al., J Thor CV Surg 2000; 119;429
![Page 17: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/17.jpg)
The BLOT StudyThe BLOT Study
86/94 were explored77/ 94 had a R0 resection ( 82%)
One postoperative death
Operative morbidity comparable to historical series of Surgery alone
Pisters K et al., J Thor CV Surg 2000; 119;429
![Page 18: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/18.jpg)
The BLOT Study
Induction carboplatin/ paclitaxel chemotherapy is safe and feasible prior to resection of clinical
early NSCLC
Pisters K et al., J Thor CV Surg 2000; 119:429-439
![Page 19: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/19.jpg)
Induction ChemotherapyInduction ChemotherapyTheThe Depierre Phase IIIDepierre Phase III StudyStudy
Surgery
Additional M IP * 2 in responders
Surgery
Induction M IP * 2
Clinical T2N0, stage II and resectable IIIA373 patients38 centers
6 years
Depierre et al., Proc ASCO 1999, abstract 1792
Adjuvant RT for pT3 and pN2
![Page 20: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/20.jpg)
OP MIP>OP
Median survival (months) 26 p=0.11 36
Survival @ 1 y (%) 73 NS 77
@ 2y (%) 52 NS 59
@ 3y (%) 41 NS 49
Operative mortality 4.5% NS 7.8%
The Depierre StudyThe Depierre Study
Depierre et al., J Clin Oncol 2001; 20: 247-53
![Page 21: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/21.jpg)
Overall SurvivalOverall Survival
11 22 5533 YearsYears44
100100
8080
6060
4040
2020
p = 0.15p = 0.15
PCTPCT
PRSPRS
|||||
_
_
_
_
_
_
_
_
_
_
66|
Reference Reference date : date :
Nov 1, 2000Nov 1, 2000
PCT arm 179 138 105 87 6433 20
PRS arm 176 129 92 67 51 3221
00Patients Patients at risk at risk
![Page 22: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/22.jpg)
Vanderbilt
Historical comparison
Induction PC Surgery alone N 34 67
Stages 2.52 <0.001 1.55
age, PFT, comorbid. =
Life Threat. Comp. (%) 27% 0.0036 6%
Reintubation 17.6% 0.0093 3%
Tracheostomy 12% 0.0042 --
Mortality 5.6% 0.045 --
Induction chemotherapyPerioperative complications ?
Roberts et al., Ann Thorac Surg 2001; 72: 885-8
![Page 23: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/23.jpg)
The Depierre Study
30 day operative mortality
MIP> S n=179 7.8%
S n=176 4.5%
NS
Breton JP et al., Proc ASCO 2001, abstract 1239
![Page 24: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/24.jpg)
The Depierre Study
30 day operative morbidity
MIP> S 39 in 33 pts
S 27 in 25 pts
NS
Breton JP et al., Proc ASCO 2001, abstract 1239
![Page 25: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/25.jpg)
The Depierre Study
BPF/ empyemas
MIP> S 10* ( 8 early + 2 late)
S 5
NS* 8/10 in N2 pts, 9/10 after pneumonectomy
Breton JP et al., Proc ASCO 2001, abstract 1239
![Page 26: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/26.jpg)
The Depierre Study
Pulmonary infections
MIP> S 10
S 11
NS
Breton JP et al., Proc ASCO 2001, abstract 1239
![Page 27: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/27.jpg)
Does induction chemotherapy (without radiation) really increase
the morbidity and mortality of lung resection ?
![Page 28: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/28.jpg)
Randomized Data Stage III Experience
![Page 29: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/29.jpg)
RESECTABLE N2 DISEASE
Pre chemotherapy
Post chemotherapy
Scans not available
![Page 30: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/30.jpg)
Induction ChemotherapyThe Roth Phase III Study (MDACC)The Roth Phase III Study (MDACC)
S urgeryn = 32
S urgeryn = 28
InductionC yE P *3
(C D D P 100 )
Resec table c /p N2 and T 3N0-1
Roth J NCI May 1994
![Page 31: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/31.jpg)
Induction ChemotherapyThe Rosell Phase III StudyThe Rosell Phase III Study
S urgeryn = 30
S urgery
Induction M IP *3n = 30
(C D D P 50 )
Resec table c /p N2 and T 3N0-1
Rosell NEJM Jan 1994
Adjuvant mediastinal RTx 50 Gy
![Page 32: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/32.jpg)
Operative risks after induction chemotherapy
Phase III data OPERATIVE MORTALITY
• Pass 1992 CS(EP)>S> RT (n=13) 0%
S>RT (n=14) 0%
• Rosell 1994 CS(MIP)>S > RT (n=30) 2/30 6.67%
S > RT (n=30) 2/30 6.67%
[all 4 deaths (2+2) were respiratory]
• Roth 1994 CS(CyEP)>S (n=28) 0*
S alone (n=32) 6* had 3 treatment related deaths
Pass, Ann Thor Surg 1992; Rosell, NEJM 1994; Roth, J NCI 1994
![Page 33: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/33.jpg)
Retrospective Data
![Page 34: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/34.jpg)
Operative risks after induction chemotherapy
MDACC
Aug 1996 to Apr 1999
335 consecutive “lobectomies or more” for NSCLC
• 76 after induction chemotherapy
• 259 surgery alone
Prospective data collection of peri-operative events
Siegenthaler et al., Ann Thor Surg 71:1105, 2001
![Page 35: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/35.jpg)
Operative risks after induction chemotherapy
MDACC (-ed)
Induction chemotherapy:
carboplatin/ paclitaxel in 93% of pts
Siegenthaler et al., Ann Thor Surg 71:1105, 2001
![Page 36: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/36.jpg)
Operative risks after induction chemotherapyOperative risks after induction chemotherapy
Chemo>Surgery (%) Surgery (%)
Mortality 1.3 5
Morbidity 44.7 51
Major Pulmonary 13.2 11.6
Tracheostomy 5.3 3.5
Empyema 0 1.2
BP Fistula 0 1.2
Transfusion 9.2 9.7
LOS, ICU admit, readmit same
Siegenthaler et al., Ann Thor Surg 71:1105, 2001
![Page 37: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/37.jpg)
Operative risks after induction chemotherapy
MDACC (-ed)
Stage specific analysis :
no difference in morbidity of CS vs. S alone
Multivariate analysis: only CAD and pneumonectomy were independent risk factors for a major postoperative event.
Siegenthaler et al., Ann Thor Surg 71:1105, 2001
![Page 38: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/38.jpg)
Operative risks after induction chemotherapy
MSKCC
Jan 1993 to Dec 1999
412 pulmonary resections after induction therapy
( ages ranged 25-82)
Preop chemotherapy: carboplatin/ paclitaxel 32%
MVP 38%
Preop radiotherapy as well : 18%
Martin J et al., Ann Thorac Surg 2001; 72: 1149-54
![Page 39: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/39.jpg)
Operative risks after induction chemotherapy
MSKCC (-ed)
297 lobectomies ( 9 sleeves, 26 bilobectomies )
97 pneumonectomies ( 20%)
18 lesser resections, 58 O&C
22% were extended resections
Martin J et al., Ann Thorac Surg 2001; 72: 1149-54
![Page 40: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/40.jpg)
Operative risks after induction chemotherapy
MSKCC (-ed)
Operative mortality
Overall 3.8%
Lobectomy 2.4%
Left Pneumonectomy 0%
Right Pneumonectomy 23.9%
• Multivariate analysis: right pneumonectomy was the only predictor of mortality
Martin J et al., Ann Thorac Surg 2001; 72: 1149-54
![Page 41: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/41.jpg)
Operative risks after induction chemotherapy
MSKCC (conclusion)
Major morbidity 26.6% , mainly respiratory
Multivariate analysis:
Increased operative blood loss, low FEV1 and right pneumonectomy were the only independent predictors of post-operative morbidity
The type of induction regimen was not a risk factor.
Martin J et al., Ann Thorac Surg 2001; 72: 1149-54
![Page 42: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/42.jpg)
Operative risks after induction chemotherapy
Does induction chemotherapy without radiationtherapy really increase the morbidity
and mortality of lung resection ?
Probably not… but most of the data published so far is either retrospective and/or comparing to historical controls ...
![Page 43: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/43.jpg)
Induction TherapyInduction Therapy
(pre-operative)
Ongoing Studies
![Page 44: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/44.jpg)
Early Stage DiseaseEarly Stage Disease
Phase III Trial INT S 9900Phase III Trial INT S 9900
cT2N0, T1N1, T2N1, T3N0, T3N1
Resection Induction carboplatin/ paclitaxel3 cycles
ResectionActivated 11.99
Accrual goal = 6001/24/03 = 279
![Page 45: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/45.jpg)
Phase III Trial INT S 9900Phase III Trial INT S 9900
“Son of BLOT”
“ BLOT or KNOT”
• Through SWOG, NCCTG, ECOG, RTOG, ACOSOG, NCIC and the CTSU.
![Page 46: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/46.jpg)
Resection
InductionCarboplatinPaclitaxel
*3
Resection
AdjuvantCarboplatinPaclitaxel
*3
Resection
Clinical StagesIA(T>2cm )
IIA-IIB, T3N1
Early Stage DiseaseEarly Stage DiseaseNATCH* NATCH* ( Neoadjuvant/ Adjuvant Taxol Carboplatin Hope)( Neoadjuvant/ Adjuvant Taxol Carboplatin Hope)
*Switzerland, Spain, Germany, Portugal, SwedenActivated 4.00
Accrual goal = 624
![Page 47: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/47.jpg)
Early Stage DiseaseEarly Stage Disease
ChEST (Chemotherapy for Early Stage Tumor)ChEST (Chemotherapy for Early Stage Tumor)
cT2N0, T1N1, T2N1, T3N0, T3N1
Resection Induction gemcitabine/ cddp3 cycles
ResectionItaly
Accrual goal = 606-712
![Page 48: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/48.jpg)
Early Stage DiseaseEarly Stage Disease
MRC Lu-22MRC Lu-22
cT1N0, T2N0, T1N1, T2N1, T3N0, T3N1
Resection Induction chemotherapy*3 cycles, Q 3weeks
ResectionUK + EORTC ( 6/02)
Activated Jan 1998Accrual goal = 450April 2002 = 239 *MVP, MIP, Cis-Vinorelbine, Cis-Gem
![Page 49: Early Stage Nsclc The Role Of Chemotherapy](https://reader035.fdocuments.us/reader035/viewer/2022081507/554b488fb4c905ff268b51b3/html5/thumbnails/49.jpg)
Will induction chemotherapy become Will induction chemotherapy become the standard of care for our patients the standard of care for our patients
with early stage disease ?with early stage disease ?
Only by completing the ongoing Only by completing the ongoing clinical trials in a timely fashion, will clinical trials in a timely fashion, will
we be able to answer this very we be able to answer this very important question.important question.