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

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

Apr 19, 2023 26 likes •268 views

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 dcembre 2016 Disclosures

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SLIDE 1

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

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SLIDE 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.

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SLIDE 3

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

10 20 30 40 50 60 70 80 90 100 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

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 20 27 21 18 15 12 9 6 3 24

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SLIDE 4

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 20 27 21 18 15 12 9 6 3 24 100 90 80 70 60 50 40 30 10 20 27 21 18 15 12 9 6 3 24

PFS (%) Nivolumab Docetaxel 1-yr PFS rate = 19% 1-yr PFS rate = 8%

OS PFS

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SLIDE 5

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 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) EGFR Mutation 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 0.5 0.25

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 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) EGFR Mutation 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 0.5 0.25

Borghaei et al. N Engl J Med 2015

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Choosing Immunotherapy

Champiat et al. CCR 2016

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Precautions for use

  • Age

Borghaei et al. N Engl J Med 2015; Herbst et al. Lancet 2016

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SLIDE 8

Precautions for use

  • Age

Borghaei et al. N Engl J Med 2015; Herbst et al. Lancet 2016

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SLIDE 9

Precautions for use

  • Autoimmune disorders

Khan et al. JAMA Oncol 2016; Johnson et al. JAMA Oncol 2015

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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

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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
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SLIDE 12

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

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SLIDE 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

– Detect any abnormality – Will serve as baseline reference

  • ECG
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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
  • ...
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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

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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
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SLIDE 17

The day of treatment

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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
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How to assess efficacy of immunotherapy?

  • Unconventional patterns of response

– Pseudoprogression – Delayed response

  • Specific criteria (irRC, iRECIST)
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How to assess efficacy of immunotherapy?

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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

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SLIDE 22

How to assess efficacy of immunotherapy?

Continue IO in case of PD on the first assessment, and maintained PS

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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

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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