Disease Burden

Colorectal Cancer

Worldwide, colorectal cancer (CRC) accounts for 10% of all cancer incidences worldwide with about 1.9 million new cases each year. Incidence rates are higher in men (10.6%) than in women (9.4%). ^[1]

Source:Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
Reference: : -Hyuna Sung PhD,Jacques Ferlay MSc, ME,Rebecca L. Siegel MPH,Mathieu Laversanne MSc,Isabelle Soerjomataram MD, MSc, PhD,Ahmedin Jemal DMV, PhD,Freddie Bray BSc, MSc, PhD: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 04 February 2021 https://doi.org/10.3322/caac.21660

Among different geographies, there is a wide variation in CRC incidence, with about 55% of the cases occurring in the developed world and rates increasing in the developing world. Notably, incidence rates have decreased 2-3% per year over the last 15 years in the United States, which appears to be primarily associated with increase in screening uptake and removal of precancerous adenoma.^[2]

About 80% of CRCs are sporadic, 15%–20% are familial and 5% are considered genetic or linked to particular genetic syndromes. About one-fourth of the patients with CRC present with advanced disease at the time of diagnosis and 35% will develop metastatic disease during the course of the disease.^[3] Metastatic colorectal cancer (mCRC) has a 5-year relative survival rate of about 12%. Drug molecules like bevacizumab have been shown to improve progression free survival and overall survival in patients with mCRC.^[4]

Figure 2: Advances in drugs for mCRC treatment and median overall survival over time^[4]
Source: Mody, K., Bekaii-Saab, T. (2017) Optimizing sequencing beyond disease progression after second-line therapy in metastatic colorectal cancer. AM J HEMATOL., 13(4), 26-30

Lung Cancer

Lung cancer is one of the most common malignancy and the most common cause of cancer-deaths worldwide. About 11.6 % (around 2 million) new cancer incidence cases and 18.4 % cancer-related deaths per year are reported due to lung cancer.^[1] The 5-year survival rate of lung cancer (19.4%) has been found to be much lower than other leading cancers.^[2] It is estimated that the number of lung cancer deaths globally will rise to 3 million in 2035 and that it would double in both women (0.5 million in 2012 to 0.9 million in 2035), and men (1.1 million in 2012 to 2.1 million in 2035).^[3] Although tobacco smoking continues to be the primary risk factor in majority of the patients, around 500,000 deaths due to lung cancer occur in the population that has never smoked. Numerous other factors may also increase the risk, which include exposure to asbestos, arsenic, radon and non-tobacco-related polycyclic aromatic hydrocarbons. ^[4]

Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancers. The bone is the most common metastatic site for NSCLC, which is followed by the brain, liver and adrenal glands.^[5] Remarkably, an increase in the proportion of NSCLC in never-smokers has been observed, especially in Asian countries, which has resulted in ‘non-smoking-associated lung cancer’ being considered a distinct disease entity, where specific molecular and genetic tumour characteristics have been identified. The 5-year survival rate for stage IV NSCLC is around 1%. ^[6,7]

Treatment options for metastatic NSCLC include systemic therapy, which includes cytotoxic and targeted agents, palliative radiotherapy for symptomatic metastases and targeted therapy. Treatment with targeted therapy may prolong progression-free survival in advanced lung cancer. Bevacizumab is a VEGF targeting monoclonal antibody drug approved for the treatment of advanced non-squamous NSCLC.

Figure 1: Timeline illustrating the development of targeted therapies and immunotherapies for the treatment of NSCLC over two decades^[8]
Source: Herbst, Roy S., Morgensztern, Daniel, Boshoff, Chris (2018). The biology and management of non-small cell lung cancer. Nature, 553, 446-454

Recurrent Glioblastoma

Glioblastoma (GBM) accounts for more than 60% of all brain tumours in adults and 50% of all gliomas in all age groups. Despite GBM being a rare tumour with global incidence of less than 10 per 100,000 people, its poor prognosis with survival rate of 14-15 months after diagnosis makes it a crucial public health issue. ^[1] The peak incidence of GBM is between 55 to 60 years. The rate of incidence of GBM is higher in men and individuals of white race, with the western world having higher incidence than the less developed world.^[2] Majority of the cases are sporadic and no risk factor accounting for a large proportion of GBMs has been identified yet. Malignant gliomas contribute to the burden of 2.5% of deaths due to cancers and are the 3^rd most common causes of death from cancer in persons 15 to 34 years of age. ^[3]

Glioblastoma has a less favorable prognosis mainly due to its high chance of tumour recurrence. Recurrence of GBM has been suggested to be inevitable after a median survival time of 32 to 36 weeks.4 More than 90% of patients with glioma showed recurrence at the original tumour location and multiple lesions developed in 5% after treatment. ^[4]

Very few cases of GBM with long-term survival have been documented and the median survival is about 14 to 15 months from the time of diagnosis.^[5] Current trends indicate that treatment of rGBM will remain multimodal in nature. Antiangiogenic agents such as bevacizumab have shown promising result as second-line treatment of recurrent GBM. ^[6]

Kidney Cancer

Renal cell carcinoma (RCC) represents over 90% of all renal malignancies. Across all populations, incidence of renal cell carcinoma (RCC) is increasing rapidly. It is among the top 10 commonest cancers in men globally.^[1] It is an aggressive type of cancer and is associated with significant mortality compared to other urological cancers. The International Agency for Research on Cancer (IARC) projects a 22% increase in RCC incidence by 2020. This steady rise is undoubtedly a global health risk.

Clear cell RCC, which is the most common histological subtype accounts for approximately 75% of the cases.^[2] Almost 30% of patients with RCC have metastatic disease at the first time of diagnosis, and 30% patients with known case of RCC restricted to the organ will eventually develop metastatic disease post the local treatment.^[3]

Along with the verified risk factors for the development of RCC, such as smoking, obesity and hypertension, incidence also correlates with age, the highest incidence being found in the sixth and seventh decades. About 80% of all RCC patients are between 40 and 69 years of age.

Clear cell renal cell carcinoma, an aggressive RCC subtype is associated with maximum rate of local invasion, metastasis, and mortality. ^[3] Numerous treatment strategies are considered to target angiogenesis for the treatment of metastatic RCC, including inhibition of VEGF protein or receptor (Figure 1). An example of a VEGF targeting drug that has been approved for the treatment of metastatic RCC is Bevacizumab.

Figure 1: Advancement in licensed therapies to treat metastatic RCC over time^[4]
Source: Janowitz, T., Welsh, S. J., Zaki, K., Mulders, P., & Eisen, T. (2013). Adjuvant Therapy in Renal Cell Carcinoma—Past, Present, and Future. Seminars in Oncology, 40(4), 482-491. doi:10.1053/j.seminoncol.2013.05.004

Cervical Cancer

According to the WHO, cervical cancer is the fourth most frequent cancer in women with an estimated 570,000 new cases in 2018 representing 6.6% of all female cancers. Approximately 90% of deaths from cervical cancer occurred in low- and middle-income countries.^[1]

Figure 1: Bar chart of region-specific incidence and mortality age-standardized rates for cancers of the cervix^[2]
Source: Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394-424. doi:10.3322/caac.21492

Human papillomavirus (HPV) infection is the predominant risk factor for cervical cancer. HPV 16 and 18 are the most common subtypes identified in cervical cancer; together they are responsible for 70% of cervical cancers worldwide. The incidence risk of cervical cancer peaks at the age of 40 to 50 years and significant number of the patients report at a later stage of the cancer.^[3,4]

Tumour angiogenesis has a potential role in the cervical cancer progression. ^[5] Recurrent and metastatic cervical cancer have limited systemic treatment choices and the primary aim to treat this disease is palliation and prolongation of survival. The standard of care regimen includes combination chemotherapy with the add-on anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody such as, bevacizumab that prevents tumour angiogenesis. ^[6]

Ovarian Cancer

Ovarian cancer is the eighth most commonly occurring cancer in women and 18th most commonly occurring cancer overall. In 2018 alone, there were nearly 300,000 new cases reported.^[1] Lifetime risk of ovarian cancer in women is one in 75, and the chance of mortality from the disease is 1 in 100. The disease typically presents at late stage when the 5-year relative survival rate ranges between 30 – 40% across the globe. ^[2]

Data suggest that each full-term pregnancy (FTP) confers a risk reduction of approximately 19% and risks among women with three or more years of OC use are 30–50% lower than those of women with little or no use.^[3]

Most patients with advanced epithelial ovarian cancer can have recurrence. ^[4] The average time for recurrence of ovarian cancer is around 18 to 24 months and disease can be fatal. Response to second-line therapy and successive lines is determined on the bases of progression-free interval after the last dose of the former line of chemotherapy. These categories are dependent on the response to platinum-based drugs (Table 1). ^[5]

Table 1: Classification of recurrent ovarian cancers^[5]
Source: Adapted from Ledermann, J. A., Raja, F. A., Fotopoulou, C., Gonzalez-Martin, A., Colombo, N., & Sessa, C. (2013). Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 24(suppl 6), vi24-vi32. doi:10.1093/annonc/mdt333

Improving the quality of life is the goal of treatment in patients with ‘platinum-resistant or refractory’ disease, whereas, multiple options are available for treating patients with ‘platinum-sensitive’ recurrence. Sequential chemotherapy schedules along with molecularly targeted therapies may prolong the median survival of patients with recurrent ovarian cancer.

Breast Cancer

Breast cancer is the most common cause of cancer in women (24.5%) worldwide, both in the developed and developing world. It is also the top causes of cancer-related mortality in women worldwide (15.5%). Based on 2020 GLOBOCAN data  , breast cancer contributes to more than 2.25 million new cases and 685000 deaths yearly. ^[1] It has been predicted that the female worldwide incidence will reach approximately 3.2 million new cases per year by 2050.^[2]

Figure 1: Pie chart representing distribution of cases and deaths of 10 most common cancers in women worldwide^[1]
Source: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394-424. doi:10.3322/caac.21492

Metastasis of breast cancer is a major reason for cancer associated mortality. About 6% of newly diagnosed cases are reported to be metastatic and approximately 30% of women initially diagnosed with earlier stages of breast cancer eventually develop recurrent, advanced or metastatic disease.^[3] Results from population-based studies show that the outcome of mBC in women is slowly but steadily improving, as risk of death is decreasing by 1–2% each year and median overall survival (OS) has increased from 18 to 24 months in recent years.^[4] The 5-year survival rate with metastatic disease is 26%. ^[5]

Treatment regimen for mBC will require an individualized approach based on multiple factors such as specific tumour biology, growth rate of disease, presence of visceral metastases, history of prior therapy and response, risk for toxicity, and patient preference. The role of angiogenesis in aiding the growth of tumour is quite accepted and its role in metastatic disease has been a part of research evaluation.

Figure 1: Bar Chart of Region-Specific Incidence and Mortality Age-Standardized Rates for Cancers of the Female Breast in 2018 ^[1]
Source: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.