How do weimplementimmunotherapyin routine practice? Lessons from the lung cancer experience

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Mitchell Haynes
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1 How do weimplementimmunotherapyin 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

2 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.

Efficacyof IO in non smallcelllungcancer CHECKMATE-017 Nivolumab Squamous Cell Carcinoma KEYNOTE-010 Pembrolizumab PD-L1 >1%, all histologies OS (%) 100 90 80 70 60 50 40 30 20 10 0 CHECKMATE-057

3 Efficacyof IO in non smallcelllungcancer CHECKMATE-017 Nivolumab Squamous Cell Carcinoma KEYNOTE-010 Pembrolizumab PD-L1 >1%, all histologies OS (%) CHECKMATE-057 Nivolumab Non-squamous 1-yr OS rate = 39% 1-yr OS rate = 51% Nivolumab Docetaxel SG OAK Atezolizumab All histologies Temps (mois) Nb à risque Atezolizumab Docetaxel Atezolizumab Docetaxel

4 Efficacyof IO in non smallcelllungcancer CHECKMATE-017 Nivolumab Squamous Cell Carcinoma CHECKMATE-017 Nivolumab Squamous Cell Carcinoma OS (%) CHECKMATE-057 Nivolumab Non-squamous 1-yr OS rate = 39% 1-yr OS rate = 51% Nivolumab Docetaxel 27 OS PFS PFS (%) CHECKMATE-057 Nivolumab Non-squamous 1-yr PFS rate = 8% 1-yr PFS rate = 19% Nivolumab Docetaxel 27

5 Choosing Immunotherapy Whatinformation do weneedto chooseimmunotherapyas 2 nd line therapy? SCC : go for it! Non-squamous: Smoking status? EGFR mutational status? Threatening tumor? N Unstratified HR (95% CI) Overall (0.62, 0.91) Age Categorization (years) < (0.62, 1.04) 65 and < (0.45, 0.89) (0.43, 1.87) Gender Male (0.56, 0.96) Female (0.58, 1.04) Baseline ECOG PS (0.44, 0.93) (0.63, 1.00) Smoking Status Current/Former Smoker (0.56, 0.86) Never Smoked (0.64, 1.61) EGFR Mutation Status Positive (0.69, 2.00) Not Detected (0.51, 0.86) Not Reported (0.51, 1.06) Borghaeiet al. N EnglJ Med 2015 Nivolumab Docetaxel

6 Choosing Immunotherapy Champiatet al. CCR 2016

7 Precautions for use Age Borghaeiet al. N EnglJ Med 2015; Herbstet al. Lancet 2016

8 Precautions for use Age Borghaeiet al. N EnglJ Med 2015; Herbstet al. Lancet 2016

9 Precautions for use Autoimmune disorders Khan et al. JAMA Oncol2016; Johnson et al. JAMA Oncol2015

10 Precautions for use Brain mets No active brainmets in the RCT Phase II showingefficacyof pembroin smallbm, asymptomatic, no corticosteroids, from melanoma and NSCLC Goldberg et al. Lancet Oncol 2016

11 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

12 What do we need before starting immunotherapy? Inform the patient Key messages : Explanations on mechanism of action Informabout the possibilityof long response, and the risk of progression Inform about the safety profile, need for reactivity Documents, patient alert card

13 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 ECG Detect any abnormality Will serve as baseline reference

14 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...

15 The day of treatment Check biological and radiological parameters Before each cycle : CBC, coagulation Liver enzymes, bilirubin Serum electrolytes Glycemia Renal function TSH, T4 every4 weeks Chest X-Ray

16 The day of treatment Once the green light has been given: In the Oncology Pharmacy: Preparation: 3 min Sterilization: min Control : 5 min In the Oncology Department: Duration of administration : 60 min Flushing: 15 min

17 The day of treatment

18 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

19 How to assess efficacy of immunotherapy? Unconventional patterns of response Pseudoprogression Delayed response Specific criteria(irrc, irecist)

20 How to assess efficacy of immunotherapy?

21 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(includedin the total tumor burden) PD must beconfirmedat least 4 weeks later

22 How to assess efficacy of immunotherapy? Continue IO in case of PD on the first assessment, and maintained PS

23 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(includedin the total tumor burden) PD must beconfirmedat least 4 weeks later Be cautiousin case of discordance between radiological and clinical response

24 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

Practice changing studies in lung cancer 2017

1 Practice changing studies in lung cancer 2017 Rolf Stahel University Hospital of Zürich Cape Town, February 16, 2018 DISCLOSURE OF INTEREST Consultant or Advisory Role in the last two years I have received