Comparisons of Non-Small Cell Lung Cancer Treatment Options: New Zealand and Australia Versus European Society for Medical Oncology (ESMO) Guidelines

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Comparisons of Non-Small Cell Lung Cancer Treatment Options: New Zealand and Australia versus European Society for Medical Oncology (ESMO) Guidelines

Version: 20th June 2019 European Society for Medical Oncology (ESMO) Treatment Guidelines

algorithm for Non-Small Cell Lung Cancer (NSCLC) as at May 2019 Chemotherapy

targeted Non-Small Cell Immunotherapy Non- Squamous Squamous

PD-L1 PD-L1≥50% PD-L1<50% ALK +ve BRAF +ve EGFR +ve ROS1+ PD-L1≥50% <50% ALK +ve BRAF +ve EGFR +ve ROS1+

Pembro w Atezo w Dabrafenib/t Atezo w bev Dabrafenib/t Chemo Gefitinib Crizotinib Chemo Pembro w chemo Crizotinib Gefitinib Crizotinib Pembrolizumab chemo chemo Crizotinib rametinib Pembrolizumab chemo rametinib

Chemo Nivolumab Nivolumab Nivolumab Alectinib Chemo Erlotinib Chemo Nivolumab Nivolumab Nivolumab Alectinib Chemo Erlotinib Chemo Chemo

Atezolizumab Pembrolizu Nivolumab Atezolizumab Pembrolizumab Atezolizumab Ceritinib Pembrolizuma Afatinib Atezolizumab Ceritinib Pembrolizumab Afatinib b Nivolumab mab

Pembrolizu Dacomitinib Rambucirumab Brigatinib Dacomitinib Atezolizumab Docetaxel Docetaxel Pembrolizumab Brigatinib mab Rambucirumab Atezolizumab Atezolizumab Atezolizumab

Rambucirumab Ramucirumab Osimertinib Nintedanib Chemo Osimertinib Docetaxel Ramucirumab Docetaxel Chemo Nintedanib Nivolumab Nivolumab Docetaxel Nintedanib Gefitinib w Gefitinib w Erlotinib Atezolizumab Erlotinib Atezolizumab Erlotinib Ramucirumab chemo Erlotinib chemo Ramucirumab Ramucirumab Erlotinib Afatinib Lorlatinib Chemo Chemo Lorlatinib Chemo Afatinib Erlotinib Chemo Erlotinib Erlotinib Chemo brigatinib Atezolizumab brigatinib Atezolizumab Afatinib Afatinib Afatinib

NOTES: 1. lines of therapy not shown for ALK/BRAF/EGFR/ROS1 2. nivolumab/ipilimumab for TMB high included in guidelines but excluded here as registration file was withdrawn from EU

Source: Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Annals of Oncology, Volume 29, Issue Supplement_4, 1 October 2018, Pages iv192–iv237 New Zealand Publicly-Funded Treatment Options compared with ESMO Guidelines for Non-Small Cell Lung Cancer as at 31 May 2019

Chemotherapy

targeted Non-Small Cell Immunotherapy Non- Squamous Squamous 30%1 70%1 PD-L1≥50% PD-L1 <50% PD-L1≥50% PD-L1<50% ALK +ve BRAF +ve EGFR +ve ROS1+ ALK +ve BRAF +ve EGFR +ve ROS1+

Pembrolizum Pembro w Atezo w Dabrafenib/tr Atezo w bev Dabrafenib/tr Chemo Gefitinib Crizotinib Chemo Pembro w chemo Crizotinib Gefitinib Crizotinib ab chemo chemo Crizotinib ametinib Pembrolizumab chemo ametinib

Chemo Nivolumab Nivolumab Nivolumab Alectinib Chemo Erlotinib Chemo Nivolumab Nivolumab Nivolumab Alectinib Chemo Erlotinib Chemo Chemo

Pembrolizum Pembrolizum Pembrolizum Pembrolizum Nivolumab Atezolizumab Atezolizumab Afatinib Atezolizumab Atezolizumab Ceritinib Afatinib ab Ceritinib ab ab ab Nivolumab

Pembrolizum Pembrolizum Rambucirum Rambucirum Atezolizumab Docetaxel Docetaxel Atezolizumab Dacomitinib Brigatinib Atezolizumab Dacomitinib ab Brigatinib ab ab ab Atezolizumab

Ramuciruma Ramuciruma Rambucirum Docetaxel Docetaxel Nivolumab Osimertinib Nintedanib Nintedanib Chemo Nivolumab Osimertinib b b Chemo ab Docetaxel

Ramuciruma Ramuciruma Gefitinib w Gefitinib w Erlotinib Erlotinib Nintedanib Erlotinib Erlotinib Atezolizumab b b Atezolizumab chemo Ramuciruma chemo b

Erlotinib Afatinib Afatinib Erlotinib Lorlatinib Chemo Erlotinib Chemo Chemo Lorlatinib Chemo Erlotinib

Afatinib Afatinib brigatinib Atezolizumab Chemo brigatinib Atezolizumab Afatinib

1. Gandhi et al, Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer, NEJM 2018 Australian Publicly-Funded Treatment Options compared with ESMO Guidelines

for Non-Small Cell Lung Cancer as at 31 May 2019 Chemotherapy

targeted Non-Small Cell Immunotherapy

Non- Squamous Squamous

PD-L1≥50% PD-L1 <50% PD-L1≥50% PD-L1<50% ALK +ve BRAF +ve EGFR +ve ROS1+ ALK +ve BRAF +ve EGFR +ve ROS1+

Chemo Nivolumab Nivolumab Nivolumab Alectinib Chemo Erlotinib Chemo Nivolumab Nivolumab Nivolumab Alectinib Chemo Erlotinib Chemo Chemo

Pembrolizuma Pembrolizum Pembrolizum Nivolumab Atezolizumab Atezolizumab Pembrolizumab Afatinib Atezolizumab Atezolizumab Ceritinib Afatinib b Ceritinib ab ab Nivolumab

Pembrolizum Rambucirum Rambucirum Atezolizumab Docetaxel Docetaxel Pembrolizumab Atezolizumab Dacomitinib Brigatinib Atezolizumab Dacomitinib Brigatinib ab ab ab Atezolizumab

Ramuciruma Ramuciruma Rambucirum Docetaxel Docetaxel Nivolumab Osimertinib Nintedanib Nintedanib Chemo Nivolumab Osimertinib b b Chemo ab Docetaxel

Ramuciruma Ramuciruma Gefitinib w Gefitinib w Erlotinib Erlotinib Nintedanib Erlotinib Erlotinib Atezolizumab b b Atezolizumab chemo Ramuciruma chemo b

Erlotinib Afatinib Afatinib Erlotinib Lorlatinib Chemo Erlotinib Chemo Chemo Lorlatinib Chemo Erlotinib

Afatinib Afatinib brigatinib Atezolizumab Chemo brigatinib Atezolizumab Afatinib

NOTES: 1. lines of therapy not shown for ALK/BRAF/EGFR/ROS1 2. nivolumab/ipilimumab for TMB high included in guidelines but excluded here as registration file was withdrawn from EU

Source: Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Annals of Oncology, Volume 29, Issue Supplement_4, 1 October 2018, Pages iv192–iv237 Australian Publicly-Funded Non-Small Cell Lung Cancer Treatment Options as at 31 May 2019

Chemotherapy Non-Small Cell 85% all lung cancer 1. Chemotherapy 1 targeted 30% 70%1 2. Afatinib Squamous Non-Squamous

14 3 3. Alectinib 30%14 70% 7% 2 Immunotherapy 12% PD-L1≥50% PD-L1 <50% 4. Atezolizumab PD-L1≥50% PD-L1<50% ALK +ve EGFR +ve 5. Ceritinib Chemo Pembrolizumab Chemo Pembrolizumab Crizotinib Gefitinib 6. Crizotinib 10 7. Erlotinib 13 13 8 8. Gefitinib Chemo Nivolumab Chemo Nivolumab Alectinib Erlotinib 4, 6 4, 6 11 7 9. Nivolumab 10. Pembrolizumab Atezolizumab Atezolizumab Ceritinib Afatinib 4, 5 4, 5 12 9 11. Osimertinib Chemo Osimertinib

Atezolizumab Chemo 4, 5

Nivolumab Atezolizumab

4, 6 4, 5

Source: Australian Pharmaceutical Benefits Scheme Nivolumab Note: Line of therapy not shown for ALK/EGFR 4, 6 1. Scarpace SL. Metastatic squamous cell non-small-cell lung cancer (NSCLC): disrupting the drug treatment paradigm with immunotherapies. Drugs in Context. 2015;4:212289. doi:10.7573/dic.212289. 2. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). American Journal of Cancer Research. 2015;5(9):2892-2911 3. Paul Hofman: ALK in Non-Small Cell Lung Cancer (NSCLC) Pathobiology, Epidemiology, Detection from Tumor Tissue and Algorithm Diagnosis in a Daily Practice; Cancers 2017, 9, 107; doi:10.3390/cancers9080107 4. https://www.pbs.gov.au/browse/medicine-listing?init (accessed Jul 18) 5. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=atezolizumab TECENTRIQ® Roche 6. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=nivolumab OPDIVO® BMS 7. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=erlotinib TARCEVA® Roche 8. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=gefitinib IRESSA ® Astra Zeneca 9. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=afatinib GILOTRIF® Boehringer-Ingelheim – Not available in New Zealand 10. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=crizotinib XALKORI® Pfizer 11. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=alectinib ALECENSA® Roche 12. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=ceritinib ZYKADIA® Novartis – Not available in New Zealand 13. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=Keytruda&r=/ KEYTRUDA® MSD 14. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=osimertinib&r=/TAGRISSO® Astra Zeneca

15. Gandhi et al, Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer, NEJM 2018 New Zealand Publicly-Funded Non-Small Cell Lung Cancer Treatment Options compared with Australia as at 31 May 2019 85% all lung 1 cancer

1 1 30% 70% Chemotherapy 1. Chemotherapy Non-Small Cell 3 2 7% 12% targeted 2. Erlotinib 70%7 30%7 Squamous Non-Squamous 3. Gefitinib Immunotherapy

PD-L1≥50% PD-L1 <50% PD-L1≥50% PD-L1<50% ALK +ve EGFR +ve

Chemo Pembrolizumab Chemo Pembrolizumab Crizotinib Gefitinib

5 Chemo Nivolumab Chemo Nivolumab Alectinib Erlotinib

Atezolizumab Atezolizumab Ceritinib Afatinib

Chemo

Atezolizumab Chemo

4, 5 Nivolumab Atezolizumab

4, 6 Source: Australian Pharmaceutical Benefits Scheme Nivolumab Note: Line of therapy not shown for ALK/EGFR 1. Scarpace SL. Metastatic squamous cell non-small-cell lung cancer (NSCLC): disrupting the drug treatment paradigm with immunotherapies. Drugs in Context. 2015;4:212289. doi:10.7573/dic.212289. 2. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). American Journal of Cancer Research. 2015;5(9):2892-2911 3. Paul Hofman: ALK in Non-Small Cell Lung Cancer (NSCLC) Pathobiology, Epidemiology, Detection from Tumor Tissue and Algorithm Diagnosis in a Daily Practice; Cancers 2017, 9, 107; doi:10.3390/cancers9080107 4. https://www.pharmac.govt.nz/tools-resources/pharmaceutical-schedule/ (accessed Jul 18) 5. http://www.medsafe.govt.nz/profs/Datasheet/t/tarcevatab.pdf TARCEVA® Roche 6. http://www.medsafe.govt.nz/profs/Datasheet/I/Iressatab.pdf IRESSA® Astra Zeneca 7. Gandhi et al, Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer, NEJM 2018 New Zealand Publicly-Funded Non-Small Cell Lung Cancer Treatment Options compared with Australia as at 31 May 2019

Australia

Chemotherapy New Zealand Afatinib Alectinib Atezolizumab Ceritinib Chemotherapy Crizotinib Erlotinib Erlotinib Gefitinib Gefitinib Nivolumab Pembrolizumab Osimertinib

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