Expectations in oncology have vastly evolved over recent decades – a cancer diagnosis does not necessarily possess the finality that it used to for some patients.1 The advent of precision medicine in oncology has renewed hope for many patients and their families, as advances in our understanding and application of biomarkers and the medicines that can be used to effectively target them has demonstrated positive long-term survival benefits for patients with common, rare or aggressive forms of cancer.2,3 In addition, our understanding of the role certain biomarkers play in disease progression is providing the opportunity to treat at an earlier stage, which can allow us to get ahead of the disease and positively impact survival. We are striving to make scientific advances that matter, and we continue to follow the science and put patients at the heart of everything we do. Now, in the face of a global pandemic, it is important that we rally together to ensure the advancements that we have made in improving patient outcomes over the past decades continue.
Extending survival through DDR inhibition
The value of treatments which exploit features of the DNA damage response (DDR) has grown significantly in recent years. We have broadened our knowledge of how disrupting DNA repair mechanisms can trigger cancer cell death in a way that has benefited those with DDR-dependent tumours, and we are now able to target tumours with homologous recombination deficiency (HRD), homologous recombination repair gene mutations (HRRm), and BRCA1/2 mutations. DDR targeted therapies have transformed the way many types of cancer are approached today, including ovarian, breast, pancreatic and prostate cancer. Some of the most well documented DDR deficiencies include BRCA1/2 gene mutations, which effect approximately 5-7% of patients with metastatic pancreatic cancer (germline BRCA-mutated) and 22% of women with ovarian cancer (germline or somatic BRCA-mutated).4,5 These cancers have long been associated with a poor prognosis and the introduction of DDR targeted therapies has changed the perception of these diseases for many.4,5,15 However, the benefit of DDR therapy has expanded into a wider population of patients including those with Homologous Recombination Deficiency (HRD) – present in 50% of women with advanced ovarian cancer, and those with mutations in HRR genes (HRRm) – which have been identified in 20-30% of men with metastatic castration-resistant prostate cancer (mCRPC).6,7 Although at the forefront of research, HRD and HRRm only represent a selection of the plethora of DDR mechanisms which could be exploited to potentially improve outcomes for patients.
For ovarian and prostate cancer, extending survival remains a key goal as five-year survival for men with mCRPC is still low and for women with advanced ovarian cancer, less than a third are expected to remain alive after five years.8,9,10,11 Through research into overall survival and sustained progression-free survival, we have reinforced our potential to make a meaningful difference for patients, bringing us closer to our goal of redefining cancer treatment.
Extending survival through early diagnosis and targeted treatment
As the leading cause of cancer-related death worldwide, research into both non-small cell (NSCLC) and small cell lung cancer (SCLC) has been central to our drive to transform the way cancer is seen and treated. Approximately 1.8 million lives were lost to lung cancer in 2018,12 signalling that a new era of transformation and discovery in this space was needed. Advancements in recent years have dramatically changed the course of lung cancer, at both the early stages, where we are helping patients live longer cancer-free, to late stage, where we are meaningfully extending survival.
Targeting lung cancer earlier is critical to improve outcomes, however, during the early stages patients typically do not experience symptoms.13 As a result, most are diagnosed at an advanced stage where survival rates are low and surgery may not be an option, presenting a significant challenge to treatment.13,14,15 Many early-stage lung cancer diagnoses are only made when the cancer is found on imaging for an unrelated condition.13,16 Even if the cancer is caught early enough, and the patient is eligible for surgery, a majority eventually develop recurrence following tumour resection and adjuvant chemotherapy.17,18 Once the tumour has spread to other parts of the body prognosis is significantly worse, and chances of a patient with NSCLC still being alive five years after diagnosis are less than 10%.15 For SCLC, a highly aggressive form of lung cancer, about two-thirds of patients are diagnosed at advanced stages and five-year survival is as low as 3%.19,20,21
Patients with lung cancer have had limited hope for long-term survival for decades.13 We need to continue to identify and diagnose patients at earlier stages and explore new, innovative possibilities in these settings. Lung cancer is a diverse disease, characterised by a variety of different genetic and molecular characteristics that promote tumour growth, and so, through biomarker testing we can learn more about each patient’s disease.22,23 Ultimately, this may help match them with the treatments that will have the optimal benefit. Other precision medicine approaches like immunotherapies, which empower the body’s immune system to recognise and respond to cancer, have shown potential and initiated a shift in the treatment paradigm for certain early-stage settings.24
Our goal is to advance our understanding and stay one step ahead of the evolving landscape to find innovative ways to help transform the lives of those with cancer. Through early and smart treatment, there is the potential for long-term disease remission and an increased possibility of cure, providing patients with precious time with their loved ones.
What does the future hold?
To look to the future, we must first address the present. Frightening evidence indicates that referrals and screening rates across the world have reduced since the start of the COVID-19 pandemic, by as much as 80%, and cancer diagnoses have dropped by nearly 50%.25,26 Yet we know that cancer does not stop during a pandemic; it may be a new normal for us, but cancer has stayed the same and poses the same challenges. These statistics raise obvious concerns as screening and early detection can drastically improve the chances of survival, and research shows delayed diagnoses could result in 10,000 additional deaths from breast and colorectal cancers alone in the next 10 years.27
We have come so far through our research to demonstrate survival benefits2,3 and we do not want to lose years of progress, even in the face of a global pandemic. We must keep up the pace, to find new and innovative ways to promote cancer detection, screening and care, working harder and smarter to further advance our knowledge in order to try and compensate. The industry, partners and the community must unite to stop cancer in its path to truly achieve the best possible survival outcomes for patients in the future and redefine cancer treatment for good.
- Cancer.org. (2020). Questions People Ask About Cancer. Available at: https://www.cancer.org/cancer/cancer-basics/questions-people-ask-about-cancer.html [Accessed September 2020].
- ESMO LBA abstract will be added when available, w/c 24 August
- Banerjee, S, et al. Maintenance olaparib for patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up (f/u) from SOLO1. Presented at ESMO 2020, virtual, August 2020
- da Cunha Colombo Bonadio et al. (2018). Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics (Sao Paulo). 2018;73(suppl 1): e450s.
- Holter et al. (2015). Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma. Journal of Clinical Oncology, 3124.
- Moschetta et al. (2016). BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Annals of Oncology, 27(8), pp.1449-1455.
- Mateo et al. (2017). DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. New England Journal of Medicine, 373(18), pp.1697–1708.
- Chemoth. Explanation of First-line and Second-line Chemotherapy Regimens. Available at: https://chemoth.com/firstline [Accessed September 2020].
- Chemoth. Evaluation of Chemotherapy Treatment. Available at: https://chemoth.com/evaluation [Accessed September 2020].
- Prostate Cancer UK. Advanced Prostate Cancer. Available at: https://prostatecanceruk.org/prostate-information/advanced-prostate-cancer [Accessed September 2020].
- Cancer.org. (2020). Survival Rates for Ovarian Cancer. Available at: https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html [Accessed September 2020].
- Gco.iarc.fr. (2018). Lung. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf [Accessed September 2020].
- LUNGevity Foundation. (2019). Screening & Early Detection. Available at https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection. [Accessed September 2020].
- American Cancer Society. Surgery for Non-Small Cell Lung Cancer. Available at: https://www.cancer.org/cancer/non-small-cell-lung-cancer/treating/surgery.html. [Accessed September 2020].
- Cancer.org. (2020). Lung Cancer Survival Rates. Available at: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html [Accessed September 2020].
- Sethi et al. Incidental Nodule Management – Should There Be a Formal Process? Journal of Thoracic Oncology, 8, pp.S494-S497.
- Pignon et al. (2008).Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. Journal of Clinical Oncology, 26, pp.3552-3559.
- Uramoto and Tanaka. (2014). Recurrence after surgery in patients with NSCLC. Translational Lung Cancer Research, 3(4), pp.242–249.
- National Cancer Institute. (n.d.). NCI Dictionary - Small Cell Lung Cancer. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer [Accessed September 2020].
- Cancer.Net. (2019). Lung Cancer - Small Cell. Available at https://www.cancer.net/cancer-types/33776/view-all [Accessed September 2020].
- Marr et al. (2016). Resected small cell lung cancer—time for more? Journal of Thoracic Disease, 8(8), pp.E755–E757.
- Korpanty et al. Biomarkers that currently affect clinical practice in lung cancer: EGFR, ALK, MET, ROS-1, and KRAS. Frontiers in Oncology, 2014(4).
- Cooper et al. (2013). Molecular biology of lung cancer. Journal of Thoracic Disease, 5(Suppl 5), pp.S479–S490.
- Cancer Research Institute. What is immunotherapy's relationship to the immune system? Available at: https://www.cancerresearch.org/immunotherapy/what-is-immunotherapy [Accessed September 2020].
- Maringe et al. (2020). The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study. The Lancet Oncology, 21(8) pp. 1023-1034.
- Kaufman et al. (2020). Changes in the Number of US Patients With Newly Identified Cancer Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic. JAMA Netw Open. 3(8)
- Sharpless. (2020). COVID-19 and cancer. Science, 368(6497), pp.1290.