How do weimplementimmunotherapyin routine practice ... · How do weimplementimmunotherapyin routine...
Transcript of How do weimplementimmunotherapyin routine practice ... · How do weimplementimmunotherapyin routine...
How do we implement immunotherapy in
routine practice? Lessons from the lung
cancer experience
Pr Alexis Cortot, M.D., Ph.D.
Thoracic Oncology Department, CHRU Lille
Institut of Biology, Lille
TAO
Paris, 9 décembre 2016
Disclosures
• Advisory boards : BMS, Roche, Astra-Zeneca, MSD
Le contenu et /ou les opinions exprimées lors de cette présentation, notamment
celui ou celle relatifs à la stratégie thérapeutique ont été réalisées en toute
indépendance.
Efficacy of IO in non small cell lung cancer
CHECKMATE-017 – Nivolumab
Squamous Cell Carcinoma
KEYNOTE-010 – Pembrolizumab
PD-L1 >1%, all histologies
CHECKMATE-057 – Nivolumab
Non-squamous
OAK – Atezolizumab
All histologies
0
10
20
30
40
50
60
70
80
90
100
0 3 6 9 12 15 18 21 24 27
SG
Temps (mois)
Nb à risque
Atezolizumab 425 363 305 248 218 188 157 74 28 1
Docetaxel 425 336 263 195 151 123 98 51 16 0
Atezolizumab
Docetaxel
Nivolumab
Docetaxel
1-yr OS rate = 51%
1-yr OS rate = 39%
OS (
%)
Time (months)
100
90
80
70
60
50
40
30
10
0
20
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Efficacy of IO in non small cell lung cancer
CHECKMATE-017 – Nivolumab
Squamous Cell Carcinoma
CHECKMATE-017 – Nivolumab
Squamous Cell Carcinoma
CHECKMATE-057 – Nivolumab
Non-squamous
CHECKMATE-057 – Nivolumab
Non-squamous
Nivolumab
Docetaxel
1-yr OS rate = 51%
1-yr OS rate = 39%
OS (
%)
Time (months)
100
90
80
70
60
50
40
30
10
0
20
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100
90
80
70
60
50
40
30
10
0
20
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PF
S (
%)
Nivolumab
Docetaxel
1-yr PFS rate = 19%
1-yr PFS rate = 8%
OS PFS
Choosing Immunotherapy
• What information do we need to choose immunotherapy as 2nd
line therapy?
� SCC : go for it!
� Non-squamous :
• Smoking status?
• EGFR mutational status?
• Threatening tumor?
N Unstratified HR (95% CI)
Overall 582 0.75 (0.62, 0.91)
Age Categorization (years)
<65 339 0.81 (0.62, 1.04)
≥65 and <75 200 0.63 (0.45, 0.89)
≥75 43 0.90 (0.43, 1.87)
Gender
Male 319 0.73 (0.56, 0.96)
Female 263 0.78 (0.58, 1.04)
Baseline ECOG PS
0 179 0.64 (0.44, 0.93)
≥1 402 0.80 (0.63, 1.00)
Smoking Status
Current/Former Smoker 458 0.70 (0.56, 0.86)
Never Smoked 118 1.02 (0.64, 1.61)
EGFRMutation Status
Positive 82 1.18 (0.69, 2.00)
Not Detected 340 0.66 (0.51, 0.86)
Not Reported 160 0.74 (0.51, 1.06)
1.0 2.0 4.0
Nivolumab Docetaxel
0.50.25
N Unstratified HR (95% CI)
Overall 582 0.75 (0.62, 0.91)
Age Categorization (years)
<65 339 0.81 (0.62, 1.04)
≥65 and <75 200 0.63 (0.45, 0.89)
≥75 43 0.90 (0.43, 1.87)
Gender
Male 319 0.73 (0.56, 0.96)
Female 263 0.78 (0.58, 1.04)
Baseline ECOG PS
0 179 0.64 (0.44, 0.93)
≥1 402 0.80 (0.63, 1.00)
Smoking Status
Current/Former Smoker 458 0.70 (0.56, 0.86)
Never Smoked 118 1.02 (0.64, 1.61)
EGFRMutation Status
Positive 82 1.18 (0.69, 2.00)
Not Detected 340 0.66 (0.51, 0.86)
Not Reported 160 0.74 (0.51, 1.06)
1.0 2.0 4.0
Nivolumab Docetaxel
0.50.25
Borghaei et al. N Engl J Med 2015
Choosing Immunotherapy
Champiat et al. CCR 2016
Precautions for use
• Age
Borghaei et al. N Engl J Med 2015; Herbst et al. Lancet 2016
Precautions for use
• Age
Borghaei et al. N Engl J Med 2015; Herbst et al. Lancet 2016
Precautions for use
• Autoimmune disorders
Khan et al. JAMA Oncol 2016; Johnson et al. JAMA Oncol 2015
Precautions for use
• Brain mets
– No active brain mets in the
RCT
– Phase II showing efficacy of
pembro in small BM,
asymptomatic, no
corticosteroids, from
melanoma and NSCLC
Goldberg et al. Lancet Oncol 2016
Precautions for use
• Concomitant therapies
– Anti-PD1/PD-L1 agents are not metabolized by cytochrome P450
– Corticosteroids
• Corticosteroids and immunosuppressive drugs may reduce efficacy of IO
• Should be avoided except for treating AEs
– Radiation therapy
• Not recommended concurrently, wait at least 2 weeks
• May increase the risk of radiation pneumonitis
• May increase efficacy of IO; ongoing trials
What do we need before starting immunotherapy?
• Inform the patient
– Key messages :
• Explanations on mechanism of action
• Inform about the possibility of long response, and the
risk of progression
• Inform about the safety profile, need for reactivity
– Documents, patient alert card
What do we need before starting immunotherapy?
• Radiological Exams
– Recent Chest CT-scan
• Will serve as baseline exam
• Looking for signs of ILD
– Recent CNS imaging
• Biological Exams
– Detect any abnormality
– Will serve as baseline reference
• ECG
The day of treatment
• Check clinical parameters
– Signs of tumor progression (PS, pain, weight loss, …)
– Signs of adverse events, including but not limited to :
• Diarrhea (colitis)
• Dyspnea (ILD)
• Fatigue (endocrinopathy)
• Rash
• ...
The day of treatment
• Check biological and radiological parameters
– Before each cycle :
• CBC, coagulation
• Liver enzymes, bilirubin
• Serum electrolytes
• Glycemia
• Renal function
– TSH, T4 every 4 weeks
– Chest X-Ray
The day of treatment
• Once the green light has been given :
– In the Oncology Pharmacy :
• Preparation : 3 min
• Sterilization : 15-30 min
• Control : 5 min
– In the Oncology Department :
• Duration of administration : 60 min
• Flushing: 15 min
The day of treatment
Monitoring of a patient treated with immunotherapy
• Clinical parameters
– Alert in case of frequent or prolonged diarrhea
– Alert in case of any unusual symptoms
• Biological parameters
• Keep monitoring even after treatment termination
• Inform patient, nurses, general practitioner, ER physicians
• « Dream team » of organ specialists implicated in the management of irAEs
How to assess efficacy of immunotherapy?
• Unconventional patterns of response
– Pseudoprogression
– Delayed response
• Specific criteria (irRC, iRECIST)
How to assess efficacy of immunotherapy?
How to assess efficacy of immunotherapy?
• Unconventional patterns of response
– Pseudoprogression
– Delayed response
• Specific criteria :
– Apperance of a new lesion is not considered
as Progressive Disease (included in the total
tumor burden)
– PD must be confirmed at least 4 weeks later
How to assess efficacy of immunotherapy?
Continue IO in case of PD on the first
assessment, and maintained PS
How to assess efficacy of immunotherapy?
• Unconventional patterns of response
– Pseudoprogression
– Delayed response
• Specific criteria :
– Apperance of a new lesion is not considered
as Progressive Disease (included in the total
tumor burden)
– PD must be confirmed at least 4 weeks later
• Be cautious in case of discordance
between radiological and clinical response
Conclusion
Implementing immunotherapy into daily practice is feasible but requires
preparation and an adapted organization :
• Correct choice of treatment
• Toxicity
– Know the immune-related toxicity
– Educate patients, nurses, practitioners
– Adapt your tools to immunotherapy (lab tests prescription, clinical reports, …)
– Identify key organ specialists
• Assessment of tumor response