How do we implement immunotherapy in routine practice? Lessons from - PowerPoint PPT Presentation

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 KEYNOTE-010 – Pembrolizumab Squamous Cell Carcinoma PD-L1 >1%, all histologies CHECKMATE-057 – Nivolumab OAK – Atezolizumab 100 Non-squamous All histologies 100 90 90 Atezolizumab 80 80 Docetaxel 70 70 60 60 50 SG 1-yr OS rate = 51% OS (%) 50 40 30 40 1-yr OS rate = 39% 20 Nivolumab 30 10 20 0 0 3 6 9 12 15 18 21 24 27 10 Temps (mois) Docetaxel Nb à risque 0 Atezolizumab 425 363 305 248 218 188 157 74 28 1 0 3 6 9 12 15 18 21 24 27 Docetaxel 425 336 263 195 151 123 98 51 16 0 Time (months)

Efficacy of IO in non small cell lung cancer CHECKMATE-017 – Nivolumab CHECKMATE-017 – Nivolumab Squamous Cell Carcinoma Squamous Cell Carcinoma OS PFS CHECKMATE-057 – Nivolumab CHECKMATE-057 – Nivolumab 100 Non-squamous 100 Non-squamous 90 90 80 80 70 70 60 60 PFS (%) 50 1-yr OS rate = 51% OS (%) 50 40 40 1-yr OS rate = 39% 30 Nivolumab 30 1-yr PFS rate = 19% 20 Nivolumab 20 10 Docetaxel 10 1-yr PFS rate = 8% Docetaxel 0 0 0 3 6 9 12 15 18 21 24 27 0 3 6 9 12 15 18 21 24 27 Time (months)

Choosing Immunotherapy • What information do we need to choose immunotherapy as 2 nd line therapy? Unstratified Unstratified HR (95% HR (95% N N CI) CI) 0.75 (0.62, 0.91) 0.75 (0.62, 0.91) Overall Overall 582 582 Age Categorization (years) Age Categorization (years) � SCC : go for it! 0.81 (0.62, 1.04) 0.81 (0.62, 1.04) <65 <65 339 339 ≥65 and <75 ≥65 and <75 0.63 (0.45, 0.89) 0.63 (0.45, 0.89) 200 200 0.90 (0.43, 1.87) 0.90 (0.43, 1.87) ≥75 ≥75 43 43 Gender Gender 0.73 (0.56, 0.96) 0.73 (0.56, 0.96) Male Male 319 319 0.78 (0.58, 1.04) 0.78 (0.58, 1.04) Female Female 263 263 Baseline ECOG PS Baseline ECOG PS � Non-squamous : 0.64 (0.44, 0.93) 0.64 (0.44, 0.93) 0 0 179 179 0.80 (0.63, 1.00) 0.80 (0.63, 1.00) ≥1 ≥1 402 402 Smoking Status Smoking Status Smoking status? Current/Former Smoker Current/Former Smoker 0.70 (0.56, 0.86) 0.70 (0.56, 0.86) 458 458 • Never Smoked Never Smoked 1.02 (0.64, 1.61) 1.02 (0.64, 1.61) 118 118 EGFR Mutation Status EGFR Mutation Status EGFR mutational status? • 1.18 (0.69, 2.00) 1.18 (0.69, 2.00) Positive Positive 82 82 0.66 (0.51, 0.86) 0.66 (0.51, 0.86) Not Detected Not Detected 340 340 Threatening tumor? 0.74 (0.51, 1.06) 0.74 (0.51, 1.06) Not Reported Not Reported 160 160 • 0.25 0.25 0.5 0.5 1.0 1.0 2.0 2.0 4.0 4.0 Nivolumab Nivolumab Docetaxel Docetaxel 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 •