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Marianne Coutts Nicolson
ES05 - Joint Session GLCC/IASLC: Hot Topics for Lung Cancer Advocates (ID 8)
- Event: WCLC 2019
- Type: Educational Session
- Track: Advocacy
- Presentations: 1
- Now Available
ES05.01 - Lung Cancer Survival: Progress and Challenges (Now Available) (ID 3175)
10:30 - 12:00 | Presenting Author(s): Marianne Coutts Nicolson
Between 1970s and 2011, many tumour 10-year survival rates increased significantly (eg prostate cancer from 25% to 84%) yet lung cancer lags behind with 5-year survival below 20%.1, 2 Most countries have no lung cancer screening programme and >80% of patients are diagnosed with advanced disease. A significant challenge for the United States lung cancer screening programme is poor uptake by low income but high risk candidates.3 To optimise results from potential curative radical radiotherapy and surgery, accurate staging of patients is vital; modern staging can improve patient selection for radical treatment, with stage 1 lung cancer 4-year overall survival (OS) increased in one study by 14.3% between 2001 and 2010, and postoperative survival improved from 51.5% to 66.5%.4 Over 80% of patients diagnosed with lung cancer are active or past cigarette smokers, and the need to maximise prevention remains. Government implemented smoking bans and funding of smoking cessation programmes are important, despite sketchy evidence for the latter being of benefit to lung cancer patients.5
Improved techniques allow accurate targeting with stereotactic ablative radiotherapy (SABR) for patients with a small tumour who are unfit for surgery. In stage III NSCLC, CT simulation results in a smaller tumour target, better dose delivery and fewer side-effects. The immune stimulating effect of radiotherapy may increase effectiveness of immunotherapy (IO) on which further research continues. Radiotherapy ablation of oligometastatic tumours is also under investigation in ongoing attempts to improve survival in advanced disease.
Systemic therapies improving survival
There has been little improvement in small cell lung cancer (SCLC) outcomes the since 1980s, but progress for the 85% of patients with non-small cell lung cancer (NSCLC) is impressive, resulting from improved understanding of tumour molecular biology. Chemotherapy combinations seemed equivalent in NSCLC until groundbreaking results showed better survival in non-squamous NSCLC who received platinum with pemetrexed over gemcitabine.6 Maintenance pemetrexed improved survival still further in patients with NSCLC stable or responsive to induction chemotherapy.
Controversy over patient selection for targeted therapy with tyrosine kinase inhibitors was resolved by the IPASS study which confirmed that testing for a sensitising EGFR mutation status was mandatory to ensure benefit.7 Patients inevitably develop resistance to EGFR TKIs and tumour rebiopsy is encouraged to determine the new molecular profile to optimise subsequent treatment. The new generation TKI osimertinib gave superior survival as first line therapy compared with erlotinib or gefitinib. In patients with ALK translocated NSCLC (approximately 5% of tumours), crizotinib was better than chemotherapy. More recently alectinib or brigatinib superceded as survival improved through their enhanced effectiveness in the CNS.8
Drugs are available to treat lung cancers with less common genetic drivers like ROS1 and BRAF but the commonest NSCLC mutation KRAS - in up to 30% cases - is not yet amenable to specific therapy, although several drugs are in development. Reflex testing by pathologists of non-squamous NSCLC is recommended with squamous tumours tested only in never smokers or mixed adenosquamous lung cancer.9 Identification of EGFR or ALK oncogene addicted lung cancers is vital to ensure delivery first line of appropriate targeted therapy since this increases patients' survival.
NSCLC response to IO drugs targeting PD-1 and PD-L1 has revolutionised systemic therapy. Nivolumab was effective in relapsed squamous NSCLC, then first line pembrolizumab superceded chemotherapy in patients with >50% PD-L1 expressing non-squamous tumours. Atezolizumab (second line) and pembrolizumab-chemo (first line) efficacy are independent of PD-L1 expression. In stage III NSCLC, patients with no tumour progression following combination chemoradiotherapy have better OS with maintenance durvalumab.10 An important feature is the durable response to IO seen in some patients, with toxicity usually manageable and less than many chemotherapies. Studies with IO as adjuvant and neoadjuvant treatments are ongoing. Since IO treatment may continue every 2-3 weeks by intravenous infusion for up to two years, there is a significant impact on pharmacy, hospital time for patients and healthcare costs. More research is ongoing to mitigate these burdens.
Improving survival in lung cancer patients remains a challenge dependent on prevention, screening, optimal surgery, modern radiotherapy and improved systemic therapies targeted through understanding the molecular biology of these heterogenous tumours. Despite clear progress to date, there is much need for improvement, offering ample opportunity for future research.
1 Quaresma M, Coleman MP, Rachet B (2015) 40-year trends in an index of survival for all cancers combined and survival adjusted for age and sex for each cancer in England and Wales 1971-2011: a population-based study. Lancet 385:1206-1218
2 Allemani C, Weir HK, Carreira H et al (2018) Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 391:1023-1075
3 Schutte S, Dietrich D, Montet X and Flahault A (2018) Particiation in lung cancer screening programs: are there gender and social differences? A systematic review. Public Health Reviews 39: 23-35
4 Boyer MJ, Williams CD, Harpole DH et al (2017) Improved survival of Stage I Non-Small Cell Lung Cancer: A VA Central Cancer Registry Analysis. J Thorac Oncol 12:1814-1823
5 Zeng L, Yu X, Xiao J, Huang Y (2019) Interventions for smoking cessation in people diagnosed with lung cancer. CochraneSystematic Review https://doi.org/10.1002/14651858. CD011751.pub3
6 Scagliotti G, Hanna N, Fossella F et al (2009) The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies. Oncologist 14:253-263
7 Mok TS, Yi-Long W, Thongprasert S, Chih-Hsin Y (2009) Gefitiib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947-957
8 Peters S, Camidge DR, Shaw AT et ak (2017) Alectinib versus crizotinib in untreated ALK-positive nono-small cell lung cancer. N Engl J Med 377:829-838
9 Planchard D, Popat S, Kerr K et al (2018) Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 29 (suppl4):iv192 - iv236
10 Antonia SJ, Villegas A, Daniel D et al (2018) Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med 379:2342-2350
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