Secuencia de cáncer gástrico, versión dos, con diapositivas de métricas.

1. Secuenciación en cáncer
gástrico metastásico
Mauricio Lema Medina
Clínica de Oncología Astorga / Clínica SOMA, Medellín

2. Wagner AD. Cochrane Database Syst Rev. 2017 Aug 29;8:CD004064. PMID: 20238327.
Quimioterapia superior a terapia de soporte

3. Key trials in metastatic gastric cancer (1st-Line)

4. 2008
REAL21
Cisplatin vs
Oxaliplatin
FU vs Capecitabine
2009
AIO2
Cisplatin vs
Oxaliplatin
2009
ML170323
FU vs Capecitabine
2010
Yun4
CX vs ECX
(P2T)
2008
Dank6
Irinotecan FULV
vs Cisplatin FULV
2010
ToGA7
Trastuzumab
+ CF
2013
EXPAND9
Cetuximab
+
Chemotherapy
2011
AVAGAST8
Bevacizumab
+
Chemotherap
y
2020
CheckMate 64910
Nivolumab + CT
1. REAL2 - Cunningham D. N Engl J Med. 2008;358(1):36–46.
2. AIO - Al-Batran SE, J Clin Oncol. 2008;26(9):1435–42.
3. ML17032 - Kang YK. Ann Oncol. 2009;20(4):666–73.
4. Yun J. Eur J Cancer. 2010;46(5):885–91.
5. TAX-325 - Van Cutsem E. J Clin Oncol. 2006;24(31):4991–7.
6. Dank M, Ann Oncol. 2008;19(8):1450–7.
7. ToGA - Bang YJ. Lancet. 2010;376(9742):687–97
8. AVAGAST - Ohtsu A. J Clin Oncol. 2011;29(30):3968–76.
9. EXPAND - Lordick F. Lancet Oncol. 2013;14(6):490–9
10. CheckMate 649 - Moehler M. ESMO Virtual Congress 2020. Abstract LBA6 PR.
11. ATTRACTION-4. Boku N. ESMO Virtual Congress 2020. Abstract LBA7 PR.
2006
TAX 3255
DCF vs CF
2020
ATTRACTION-411
Nivolumab + CT
Key trials in metastatic gastric cancer (1st-Line)
Cisplatin vs Oxaliplatin
Oxaliplatin, non-inferior
Different toxicity profile
Oxaliplatin, less toxic
Oxaliplatin, probably, superior ≥ 65 yo

5. 2008
REAL21
Cisplatin vs
Oxaliplatin
FU vs Capecitabine
2009
AIO2
Cisplatin vs
Oxaliplatin
2009
ML170323
FU vs Capecitabine
2010
Yun4
CX vs ECX
(P2T)
2008
Dank6
Irinotecan FULV
vs Cisplatin FULV
2010
ToGA7
Trastuzumab
+ CF
2013
EXPAND9
Cetuximab
+
Chemotherapy
2011
AVAGAST8
Bevacizumab
+
Chemotherap
y
2020
CheckMate 64910
Nivolumab + CT
1. REAL2 - Cunningham D. N Engl J Med. 2008;358(1):36–46.
2. AIO - Al-Batran SE, J Clin Oncol. 2008;26(9):1435–42.
3. ML17032 - Kang YK. Ann Oncol. 2009;20(4):666–73.
4. Yun J. Eur J Cancer. 2010;46(5):885–91.
5. TAX-325 - Van Cutsem E. J Clin Oncol. 2006;24(31):4991–7.
6. Dank M, Ann Oncol. 2008;19(8):1450–7.
7. ToGA - Bang YJ. Lancet. 2010;376(9742):687–97
8. AVAGAST - Ohtsu A. J Clin Oncol. 2011;29(30):3968–76.
9. EXPAND - Lordick F. Lancet Oncol. 2013;14(6):490–9
10. CheckMate 649 - Moehler M. ESMO Virtual Congress 2020. Abstract LBA6 PR.
11. ATTRACTION-4. Boku N. ESMO Virtual Congress 2020. Abstract LBA7 PR.
2006
TAX 3255
DCF vs CF
2020
ATTRACTION-411
Nivolumab + CT
Key trials in metastatic gastric cancer (1st-Line)
FU vs Capecitabine
Capecitabine non inferior to FU (or slightly superior)
Capecitabine: High occurrence of hand-foot syndrome
2008
REAL21
2009
ML170323
FU vs Capecitabine

6. 2008
REAL21
Cisplatin vs
Oxaliplatin
FU vs Capecitabine
2009
AIO2
Cisplatin vs
Oxaliplatin
2009
ML170323
FU vs Capecitabine
2010
Yun4
CX vs ECX
(P2T)
2008
Dank6
Irinotecan FULV
vs Cisplatin FULV
2010
ToGA7
Trastuzumab
+ CF
2013
EXPAND9
Cetuximab
+
Chemotherapy
2011
AVAGAST8
Bevacizumab
+
Chemotherap
y
2020
CheckMate 64910
Nivolumab + CT
1. REAL2 - Cunningham D. N Engl J Med. 2008;358(1):36–46.
2. AIO - Al-Batran SE, J Clin Oncol. 2008;26(9):1435–42.
3. ML17032 - Kang YK. Ann Oncol. 2009;20(4):666–73.
4. Yun J. Eur J Cancer. 2010;46(5):885–91.
5. TAX-325 - Van Cutsem E. J Clin Oncol. 2006;24(31):4991–7.
6. Dank M, Ann Oncol. 2008;19(8):1450–7.
7. ToGA - Bang YJ. Lancet. 2010;376(9742):687–97
8. AVAGAST - Ohtsu A. J Clin Oncol. 2011;29(30):3968–76.
9. EXPAND - Lordick F. Lancet Oncol. 2013;14(6):490–9
10. CheckMate 649 - Moehler M. ESMO Virtual Congress 2020. Abstract LBA6 PR.
11. ATTRACTION-4. Boku N. ESMO Virtual Congress 2020. Abstract LBA7 PR.
2006
TAX 3255
DCF vs CF
2020
ATTRACTION-411
Nivolumab + CT
Key trials in metastatic gastric cancer (1st-Line)
Triplets vs Doublets
Higher response with triplets
Higher toxicity with triplets
Conflicting OS results
Consider triplets in < 55 yo AND PS 0/1
2009
ML170323
FU vs Capecitabine
2010
Yun4
CX vs ECX
(P2T)
2006
TAX 3255
DCF vs CF

7. 2008
REAL21
Cisplatin vs
Oxaliplatin
FU vs Capecitabine
2009
AIO2
Cisplatin vs
Oxaliplatin
2009
ML170323
FU vs Capecitabine
2010
Yun4
CX vs ECX
(P2T)
2008
Dank6
Irinotecan FULV
vs Cisplatin FULV
2010
ToGA7
Trastuzumab
+ CF
2013
EXPAND9
Cetuximab
+
Chemotherapy
2011
AVAGAST8
Bevacizumab
+
Chemotherap
y
2020
CheckMate 64910
Nivolumab + CT
1. REAL2 - Cunningham D. N Engl J Med. 2008;358(1):36–46.
2. AIO - Al-Batran SE, J Clin Oncol. 2008;26(9):1435–42.
3. ML17032 - Kang YK. Ann Oncol. 2009;20(4):666–73.
4. Yun J. Eur J Cancer. 2010;46(5):885–91.
5. TAX-325 - Van Cutsem E. J Clin Oncol. 2006;24(31):4991–7.
6. Dank M, Ann Oncol. 2008;19(8):1450–7.
7. ToGA - Bang YJ. Lancet. 2010;376(9742):687–97
8. AVAGAST - Ohtsu A. J Clin Oncol. 2011;29(30):3968–76.
9. EXPAND - Lordick F. Lancet Oncol. 2013;14(6):490–9
10. CheckMate 649 - Moehler M. ESMO Virtual Congress 2020. Abstract LBA6 PR.
11. ATTRACTION-4. Boku N. ESMO Virtual Congress 2020. Abstract LBA7 PR.
2006
TAX 3255
DCF vs CF
2020
ATTRACTION-411
Nivolumab + CT
Key trials in metastatic gastric cancer (1st-Line)
Biologics
Cetuximab and Bevacizumab: no rôle
Trastuzumab improves OS in HER2+
2009
ML170323
FU vs Capecitabine
2010
Yun4
CX vs ECX
(P2T)
2006
TAX 3255
DCF vs CF
2010
ToGA7
Trastuzumab
+ CF
2013
EXPAND9
Cetuximab
+
Chemotherapy
2011
AVAGAST8
Bevacizumab
+
Chemotherap
y

8. 2008
REAL21
Cisplatin vs
Oxaliplatin
FU vs Capecitabine
2009
AIO2
Cisplatin vs
Oxaliplatin
2009
ML170323
FU vs Capecitabine
2010
Yun4
CX vs ECX
(P2T)
2008
Dank6
Irinotecan FULV
vs Cisplatin FULV
2010
ToGA7
Trastuzumab
+ CF
2013
EXPAND9
Cetuximab
+
Chemotherapy
2011
AVAGAST8
Bevacizumab
+
Chemotherap
y
2020
CheckMate 64910
Nivolumab + CT
1. REAL2 - Cunningham D. N Engl J Med. 2008;358(1):36–46.
2. AIO - Al-Batran SE, J Clin Oncol. 2008;26(9):1435–42.
3. ML17032 - Kang YK. Ann Oncol. 2009;20(4):666–73.
4. Yun J. Eur J Cancer. 2010;46(5):885–91.
5. TAX-325 - Van Cutsem E. J Clin Oncol. 2006;24(31):4991–7.
6. Dank M, Ann Oncol. 2008;19(8):1450–7.
7. ToGA - Bang YJ. Lancet. 2010;376(9742):687–97
8. AVAGAST - Ohtsu A. J Clin Oncol. 2011;29(30):3968–76.
9. EXPAND - Lordick F. Lancet Oncol. 2013;14(6):490–9
10. CheckMate 649 - Moehler M. ESMO Virtual Congress 2020. Abstract LBA6 PR.
11. ATTRACTION-4. Boku N. ESMO Virtual Congress 2020. Abstract LBA7 PR.
2006
TAX 3255
DCF vs CF
2020
ATTRACTION-411
Nivolumab + CT
Key trials in metastatic gastric cancer (1st-Line)
Immuno-oncology
Nivolumab improves PFS
Nivolumab improves OS (mainly, in PD-L1 ≥ 5%)
No peer-reviewed publication (as of 02.2021)
No regulatory approval (Colombia)
2008
REAL21
Cisplatin vs
Oxaliplatin
FU vs Capecitabine
2009
ML170323
FU vs Capecitabine
2020
CheckMate 64910
Nivolumab + CT
2020
ATTRACTION-411
Nivolumab + CT

9. 2008
REAL21
Cisplatin vs
Oxaliplatin
FU vs Capecitabine
2009
AIO2
Cisplatin vs
Oxaliplatin
2009
ML170323
FU vs Capecitabine
2010
Yun4
CX vs ECX
(P2T)
2008
Dank6
Irinotecan FULV
vs Cisplatin FULV
2010
ToGA7
Trastuzumab
+ CF
2013
EXPAND9
Cetuximab
+
Chemotherapy
2011
AVAGAST8
Bevacizumab
+
Chemotherap
y
2020
CheckMate 64910
Nivolumab + CT
1. REAL2 - Cunningham D. N Engl J Med. 2008;358(1):36–46.
2. AIO - Al-Batran SE, J Clin Oncol. 2008;26(9):1435–42.
3. ML17032 - Kang YK. Ann Oncol. 2009;20(4):666–73.
4. Yun J. Eur J Cancer. 2010;46(5):885–91.
5. TAX-325 - Van Cutsem E. J Clin Oncol. 2006;24(31):4991–7.
6. Dank M, Ann Oncol. 2008;19(8):1450–7.
7. ToGA - Bang YJ. Lancet. 2010;376(9742):687–97
8. AVAGAST - Ohtsu A. J Clin Oncol. 2011;29(30):3968–76.
9. EXPAND - Lordick F. Lancet Oncol. 2013;14(6):490–9
10. CheckMate 649 - Moehler M. ESMO Virtual Congress 2020. Abstract LBA6 PR.
11. ATTRACTION-4. Boku N. ESMO Virtual Congress 2020. Abstract LBA7 PR.
2006
TAX 3255
DCF vs CF
2020
ATTRACTION-411
Nivolumab + CT
Key trials in metastatic gastric cancer (1st-Line)

10. MEDIAN OS
ACROSS TRIALS
10 month
ECF1
ECX1
EOF1
EOX1
FO2
CF3
DCF3
FI4
TCF5
NCF6
10 month
E: Epirubicin, C: Cisplatin, F: Fluorouracil, X: Capecitabine, O: Oxaliplatin, D: Docetaxel, I: Irinotecan, T: Trastuzumab (HER2+), N: Nivolumab (PD-L1 CPS ≥ 5%)
1. REAL2 - Cunningham D. N Engl J Med. 2008;358(1):36–46, 2. AIO - Al-Batran SE, J Clin Oncol. 2008;26(9):1435–42., 3. TAX-325 - Van Cutsem E. J Clin Oncol. 2006;24(31):4991–7. 4. Dank
M, Ann Oncol. 2008;19(8):1450–7. 5. ToGA - Bang YJ. Lancet. 2010;376(9742):687–97. 6. CheckMate 649 - Moehler M. ESMO Virtual Congress 2020. Abstract LBA6 PR.
9.9
9.9
9.3
11.2
10.7
8.6
9.2
9.0
13.8
14.4

11. Primera línea en cáncer gástrico
Platino + Fluoropirimidina
(Backbone)
Cisplatino u oxaliplatino
FU o capecitabina
Adicionar
Trastuzumab si HER2+
Considerar adición de
antraciclina o taxano
en jóvenes, buen PS
Considerar IO, cuando
esté disponible
Considerar
monoagente (FU-like)
si no tolera poliquimio
Matices

12. 2LMETASTATICGASTRIC CANCER
Key Trials
Iri or Docetaxel vs BSC
2012
Kang2
Ramucirumab + Paclitaxel vs
Paclitaxel
2014
RAINBOW4
Irinotecan vs BSC
2011
AIO1
Docetaxel vs BSC
2013
Ford3
1. AIO - Thuss-Patience PC. Eur J Cancer. 2011;47(15):2306–14.
2. Kang JH. J Clin Oncol. 2012;30(13):1513–8.
3. Ford H. J Clin Oncol. 2013; 30. suppl 34 (abstr LBA4).
4. RAINBOW - Wilke H. Lancet Oncol. 2014 Oct;15(11):1224-35.
CT in 2L
2L improves OS in PS0/1
2L improves symptom control
Irinotecan or taxane-based
Ramucirumab + paclitaxel one SoC

13. MEDIAN OS
ACROSS TRIALS
I I or D D P+R
6
4
2
8
1. AIO - Thuss-Patience PC. Eur J Cancer. 2011;47(15):2306–14. 2. Kang JH. J Clin Oncol. 2012;30(13):1513–8. 3. Ford H. J Clin Oncol. 2013; 30. suppl 34 (abstr
LBA4). 4. RAINBOW - Wilke H. Lancet Oncol. 2014 Oct;15(11):1224-35.
4.0
5.3 5.2
9.6
D: Docetaxel, I: Irinotecan, P: Paclitaxel, R: Ramucirumab
Months

14. Propuesta de secuencia en cáncer gástrico
metastásico
Platino + Fluoropirimidina
(Backbone)
Cisplatino u oxaliplatino1
FU o capecitabina1
Adicionar
Trastuzumab si
HER2+3
Considerar adición de
antraciclina o taxano
en jóvenes, buen PS2
Considerar adicionar
IO, cuando esté
disponible4,5
Considerar
monoagente (FU-like)
si no tolera poliquimio
Progresión (2L)– Considerar
Ramucirumab + Paclitaxel7
Progresión (3L)– Considerar
Irinotecán6
Mauricio Lema Medina, 2021
IO: anti PD1 (ie, nivolumab / pembrolizumab)
PS: Desempeño
Joven: ≤ 55 años, y cambiando.
1. REAL2 - Cunningham D. N Engl J Med. 2008;358(1):36–46.
2. TAX-325 - Van Cutsem E. J Clin Oncol. 2006;24(31):4991–7.
3. ToGA - Bang YJ. Lancet. 2010;376(9742):687–97
4. CheckMate 649 - Moehler M. ESMO Virtual Congress 2020. Abstract LBA6 PR.
5. ATTRACTION-4. Boku N. ESMO Virtual Congress 2020. Abstract LBA7 PR.
6. AIO - Thuss-Patience PC. Eur J Cancer. 2011;47(15):2306–14.
7. RAINBOW - Wilke H. Lancet Oncol. 2014 Oct;15(11):1224-35.