Pseudo- et Hyperprogression tumorale

Esma Saada-Bouzid, MD, PhD

Medical Oncologist, CAL, Nice

« Avec le soutien organisationnel de Bristol-Myers Squibb »

Liens d’intérêt

Invitations congrès:

Merck Serono, Astra Zeneca, MSD

Astra Zeneca, Merck Serono, Investigateurs:

BMS, Ipsen, Astra Zeneca, MSD

Advisory Board:

BMS, Astra Zeneca, Merck Serono

« Le contenu et/ou les opinions exprimées lors de cette présentation,

notamment celui ou celle(s) relatifs à la stratégie thérapeutique ont

été réalisés en toute indépendance »

Patterns of response and progression under

immunotherapy

Borcoman et al, Ann Oncol 2019

Pseudoprogression

Pseudo-progression

Patients experiencing an objective response following disease

progression

Question of continuing treatment beyond disease progression ?

Lung adenocarcinoma

Hochmair, Lung cancer, 2017

Baseline First CT scan Second CT scan

Rates of pseudo-

progression Rates of pseudoPD Range Ref

Melanoma

Nivolumab 8,1% (17/210)

4,6-8,3%Robert 2015

Nivolumab 8,3% (10/120) Weber 2015

Anit-PD1 4,6% (245/526) Long 2017

NSCLC

Nivolumab 3,4% (4/117)

1,8-6,9%

Rizvi 2015

Nivolumab 5,5% (16/292) Borghaei 2015

Nivolumab 6,9% (9/131) Brahmer 2015

Atezolizumab 3,6% (12/332) Gandara 2017

Anti-PD1 1,9% (10/535) Kazandjian 2017

Anti-PD1 1,8% (3/166) Katz 2018

Anti-PD1/PDL1 5% (8/160) Tazdait 2018

HNSCC

Nivolumab 1,3% (3/240) 1,3% Haddad 2017

RCC

Nivolumab 7,1% (12/168)

4,9-7,1%George 2016

Nivolumab 4,9% (20/406) Escudier 2017

Urothelial

carcinoma

Nivolumab 9,1% (24/265)

1,6-9,1%Sharma 2017

Atezolizumab 1,6% (5/310) Necchi 2017

According to Borcoman et al, Annals of Oncol 2018

Pseudo-progression

Pseudo-progression remains a rare event and the

majority of patients who have disease progression have a

real progression

Decision of treatment beyond progression should be

only taken in carefully selected patients who

experience a clinical benefit and who have not

experienced severe toxicities

Hyperprogression

05/08/2018

avant anti-PD1

C1: 24/08/2018

C2: 07/09/2018

08/09/2018

(C2J2)

05/10/2018

C4J1

12/11/2018

C6J11

Hyper-progressive disease

Clinical observations of patients whose disease seemed

to grow faster after the initiation of immunotherapy

Champiat, Nature Reviews Clinical Oncology, 2018

Crossing survival curves in clinical trial

Champiat, Nature Reviews Clinical Oncology, 2018

Criteria used in the literature to define

hyperprogression

Borcoman et al, Ann Oncol 2019

Hyperprogression and RM HNSCC

Saada-Bouzid et al, Ann Oncol 2017

10/34=29%

Rates of hyperprogression in patients

receiving CPI

Borcoman et al, Ann Oncol 2019

[3,8% -29,4%]

HPD: biological hypothesis

Salvage Chemotherapy post immunotherapy

N=82

ORR=31%

CR + PP + SD = 58%

Median OS= 7.8 m

Median PFS= 3.6 m

⚫ ORR>> than reported ORR in this setting (5% for MTX, 16% for taxans)

Clinical implications

In case of rapid progression, an early clinical and imaging

assessment should be carried out in order to rapidly switch

to another potential effective treatment, especially in case

of clinical deterioration

Conclusion

Pseudoprogression Hyperprogression

Progression followed by

response

Acceleration of the tumor growth

kinetic

Rare event in advanced

carcinoma

Not rare (≈15%)

Continue anti-PD1 only in

selected cases with clinical

benefit

Early assessment and switch for

chemotherapy