The road less travelled: what options are available for patients with advanced squamous cell carcinoma?

Transcription

1 Robert Pirker Medical University of Vienna Vienna, Austria The road less travelled: what options are available for patients with advanced squamous cell carcinoma?

2 Disclosures Honoraria for advisory board/consulting AstraZeneca Boehringer Ingelheim Clovis Eli Lilly Pfizer Roche Speaker s fee AstraZeneca Boehringer Ingelheim Eli Lilly Data safety monitoring board Merck Sharp & Dohme Genmab Regeneron Synta

3 Learning objective After this presentation, participants will be able to describe current and emerging treatment modalities (targeted, anti-angiogenesis, immunotherapy) for advanced squamous NSCLC summarize their efficacy and safety in recent clinical trials

4 Case discussion A 65-year-old male, former smoker Cough for 3 months, ECOG-1 Diagnosis: squamous cell carcinoma stage IV ECOG-1, Eastern Cooperative Oncology Group performance status score of 1. Courtesy of R. Pirker.

5 Case A (continued) Courtesy of R. Pirker.

6 Case A (continued) 65-year-old male, former smoker Cough for 3 months, ECOG-1 Diagnosis: squamous cell carcinoma stage IV Treatment? EGFR IHC score 200; PD-L1 5% EGFR, epidermal growth factor receptor; IHC, immunohistochemistry; PD-L1, programmed death-ligand 1. Courtesy of R. Pirker.

7 Question 1 Which treatment would you start? 1. Cisplatin + gemcitabine 2. Cisplatin + gemcitabine + necitumumab 3. Platin + gemcitabine + bevacizumab 4. Pembrolizumab 5. Other

8 Metastatic NSCLC: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up 1 PD-L1 50% PS Pembrolizumab 2 PS 1 < 70 years Squamous NSCLC (stage IV) No driver mutation PS 2 < 70 years or PS 0 2 > 70 years PS cycles Platinum-based doublet a Necitumumab-cisplatingemcitabine if IHC EGFR +ve 4 6 cycles Carboplatin based doublet a Single agent (gemcitabine, vinorelbine, docetaxel) BSC a Cisplatin/gemcitabine; cisplatin/docetaxel; cisplatin/vinorelbine; carboplatin/paclitaxel; carboplatin/nab-paclitaxel. PS, performance status. 1. Based on Novello S, et al. Ann Oncol. 2016;27(Suppl 5):v Reck, M. et al. N Eng J Med. 2016;375:

9 OS (%) Cisplatin/gemcitabine ± necitumumab: SQUIRE Overall survival (n = 1,093) Number at risk Necitumumab + gemcitabine and cisplatin Necitumumab + gemcitabine and cisplatin Gemcitabine and cisplatin Censored patients Necitumumab* + gemcitabine and cisplatin (n = 545) HR: 0.84 (95% CI: ); p = 0.01 Median survival 11.5 months versus 9.9 months, 1-year survival rate 48% versus 43% Gemcitabine and cisplatin (n = 548) Patients censored, n (%) 127 (23) 106 (19) Median OS, months (95% CI) 11.5 ( ) 9.9 ( ) Stratified p value (log-rank) 0.01 Stratified HR (95% CI) 0.84 ( ) * 800 mg i.v. days 1 and Gemcitabine and cisplatin OS, overall survival. Reproduced from Thatcher N, et al. Lancet Oncol. 2015;16: , Elsevier Ltd. All rights reserved.

10 OS (%) Cisplatin/gemcitabine ± necitumumab: SQUIRE Overall survival (n = 935: subpopulation of patients with EGFR protein expression) Median OS, months Necitumumab + gemcitabine cisplatin 11.7 Gemcitabine cisplatin 10.0 HR (95% CI), p value 0.79 ( ), p = Necitumumab + gemcitabine cisplatin Gemcitabine cisplatin Time since randomization (months) HR: 0.79 (95% CI: ); p = Median survival 11.7 months versus 10.0 months Reproduced from Paz-Ares L, et al. Ann Oncol. 2016;27: , Oxford University Press.

11 Case discussion B 73-year-old female, never smoker Increasing dyspnoea at exertion during last two months; ECOG-1 CT scan CT, computerized tomography. Courtesy of R. Pirker.

12 Case B (continued) Courtesy of R. Pirker.

13 Case B (continued) 73-year-old female, never smoker Increasing dyspnoea at exertion during last two months; ECOG-1 CT scan: lesions in right & left lung, mediastinal lymph node, cervical lymph node Treatment? Bronchoscopy Diagnosis: squamous cell carcinoma of the lung stage IV, no driver mutation Courtesy of R. Pirker.

14 Question 2 Which treatment would you start? 1. Gemcitabine or vinorelbine 2. Carboplatin + gemcitabine, or carboplatin + vinorelbine 3. Carboplatin + paclitaxel 4. Pembrolizumab 5. Other

15 Lung cancer therapy in elderly patients: factors to be considered Patient-related factors age and life expectancy gender performance status co-morbidity, organ functions geriatric syndromes functional status convenience of administration side effects of drugs polypharmacy patient preference Tumour-related factors histological subtype molecular characteristics tumour stage tumour growth Costs, cost effectiveness value-based judgements Courtesy of R. Pirker.

16 First-line chemotherapy in elderly patients with advanced NSCLC phase 3 trials Vinorelbine > BSC (ELVIS) 1 Vinorelbine = gemcitabine = gemcitabine/vinorelbine (MILES) 2 Vinorelbine + gemcitabine > vinorelbine 3 Carboplatin + paclitaxel > vinorelbine or gemcitabine 4 Single agent ± cisplatin (MILES 3 and MILES 4) 5 BSC, best supportive care. 1. Gridelli C, et al. J Natl Cancer Inst.1999;91: Gridelli C, et al. J Natl Cancer Inst. 2003;95: Frasci G, et al. J Clin Oncol. 2000;13: Quoix E, et al. Lancet. 2011;378: Gridelli C, et al. J Clin Oncol. 2017;35 Suppl 15:abstract 9002.

17 Case B (continued) 73-year-old female, never smoker Increasing dyspnoea at exertion during last two months; ECOG-1 CT scan: lesions in right and left lung, mediastinal lymph node, cervical lymph node Chemotherapy (2 cycles of carboplatin + gemcitabine; 2 cycles of gemcitabine) resulted in symptom relief and radiological partial response haematotoxicity (leucopenia, anaemia) Bronchoscopy Diagnosis: squamous cell carcinoma of the lung stage IV Courtesy of R. Pirker.

18 Case B (continued) Before chemotherapy After chemotherapy Courtesy of R. Pirker.

19 Patients (%) Patients (%) Predicting chemotherapy toxicity in elderly patients Patients with lung (29%), GI (27%), gynaecologic (17%), breast (11%), GU (10%) or other (6%) cancers Toxicity grade 3 5 Predictive model based on age 72 hearing (fair or worse) haemoglobin < 11 (male) or < 10 g/dl (female) falls in last six months (one or more) creatinine clearance < 34 ml/min walking one block (limited, somewhat, or a lot) cytoxic drugs (dosing; number) taking medications (some help/unable) decreased social activity cancer type GI or GU Main toxicities leucopenia, anaemia fatigue, infection, dehydration Low Medium High Total risk score <70 MD-rated KPS (%) GI, gastrointestinal; GU, genitourinary; MD, physician; KPS, Karnofsky performance status. Hurria A, et al. J Clin Oncol. 2011;29:

20 Chemotherapy in elderly patients with advanced NSCLC Individualized therapy based on evidence, personal experience (judgement), and patient preference Performance status, co-morbidity, organ function, geriatric syndromes, social support, life expectancy, patient preference Chemotherapy protocols for first-line therapy fit patients: doublet or single agent vulnerable patients: consider single agent frail patients: no chemotherapy Expect increased toxicity Enhanced supportive care prophylaxis of emesis, obstipation, infection, and dehydration Aged over 80: no general recommendations Courtesy of R. Pirker.

21 Case discussion C 50-year-old male, heavy smoker Pain in left shoulder for several weeks; ECOG-1 CT scan: lesions in left upper lung, suspicious lesion in right adrenal gland CT-guided biopsy of the left lung Diagnosis: squamous cell carcinoma of the left lung, stage IV (?) PD-L1 negative Chemotherapy plus thoracic radiotherapy Courtesy of R. Pirker.

22 Case C (continued) Before chemotherapy After chemotherapy Courtesy of R. Pirker.

23 Question 3 Progression after chemotherapy (cisplatin + vinorelbine) and radiotherapy: which treatment would you start? 1. Docetaxel 2. Docetaxel + ramucirumab 3. Immune checkpoint inhibitor 4. Afatinib 5. Other

24 Metastatic NSCLC: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up Progression after front-line treatment (SCC stage IV) PS 0 2 PS 3 4 Nivolumab Pembrolizumab if PD-L1 > 1% Docetaxel Docetaxel + ramucirumab Erlotinib Afatinib BSC SCC, squamous cell carcinoma. Based on Novello S, et al. Ann Oncol. 2016;27(Suppl 5):v1-27.

25 Recent advances in pre-treated patients with advanced squamous NSCLC Docetaxel + ramucirumab (REVEL) 1 Afatinib in squamous cell NSCLC (LUX-Lung 8) 2 Nivolumab 3 Pembrolizumab 4 Atezolizumab 5 1. Garon EB, et al. Lancet. 2014;384: Soria JC, et al. Lancet Oncol. 2015;16: Brahmer J, et al. N Eng J Med. 2015;373: Herbst RS, et al. Lancet. 2016;387: Rittmeyer A, et al. Lancet. 2017;389:

26 OS (%) Docetaxel ± ramucirumab (10 mg/kg): REVEL Ramucirumab + docetaxel Placebo + docetaxel Censored Time (months) Number at risk Ramucirumab + docetaxel Placebo + docetaxel OS: HR 0.86 (95% CI: ), p = Median (95% CI) Censoring rate (%) Ramucirumab + docetaxel 10.5 months ( ) 31.8 Placebo + docetaxel 9.1 months ( ) 27.0 Ramucirumab vs placebo, Stratified HR (95% CI), p value 0.86 ( ), p = Reproduced from Garon EB, et al. Lancet 2014;384: , Elsevier Ltd. All rights reserved.

27 OS (%) Afatinib versus erlotinib in squamous cell carcinoma of the lung: LUX-Lung Afatinib Erlotinib Afatinib Time (months) Number at risk Afatinib Erlotinib OS: HR 0.81 (95% CI: ), p = Erlotinib Median OS, months (95% CI) 7.9 ( ) 6.8 ( ) Soria JC, et al. Lancet Oncol. 2015;16:

28 OS (% of patients) OS (% of patients) Nivolumab versus docetaxel in advanced NSCLC: overall survival Nivolumab Docetaxel Nivolumab Docetaxel Time (months) Number at risk Nivolumab Docetaxel Squamous 1 HR 0.59 (95% CI: ) p < Time (months) Number at risk Nivolumab Docetaxel Adenocarcinoma 2 HR 0.73 (95% CI: ) p = Brahmer J, et al. N Eng J Med. 2015;373: Borghaei H, et al. N Eng J Med. 2015;373:

29 OS (%) OS (%) Pembrolizumab (2 or 10 mg/kg) versus docetaxel in advanced NSCLC: overall survival Number at risk Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel Time (months) Number at risk Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel PD-L1 50% Pembrolizumab 10 mg/kg every 3 weeks: HR 0.50 (95% CI: ); p < Pembrolizumab 2 mg/kg every 3 weeks: HR 0.54 (95% CI: ); p = All patients Pembrolizumab 10 mg/kg every 3 weeks: HR 0.61 (95% CI: ); p < Pembrolizumab 2 mg/kg every 3 weeks: HR 0.71 (95% CI: ); p = Reproduced from Herbst RS, et al. Lancet. 2016;387: , Elsevier Ltd. All rights reserved.

30 Conclusions Necitumumab added to first-line chemotherapy with cisplatin plus gemcitabine improves survival of patients with advanced squamous cell carcinoma of the lung Elderly patients benefit from first-line chemotherapy with single agents or well-tolerated doublets, but require enhanced supportive care measures Ramucirumab added to docetaxel improves survival of patients with advanced NSCLC who have previously been treated with chemotherapy

31 Relative risk Relative risk Benefits of stopping smoking: UK Million Women Study Death from any cause 4 Death from lung cancer Current smokers Women who never smoked Current smokers Women who never smoked Age of former smokers at cessation (year) Age of former smokers at cessation (year) Jha P, Peto R. N Eng J Med. 2014;370:60-8.

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