A more positive future for those diagnosed with triple negative breast cancer?

Friday 4th February marks World Cancer Day and we want to highlight the potential benefits of leveraging Real World Evidence (RWE) to increase future treatment options for patients who have been diagnosed with Triple Negative Breast Cancer (TNBC).

Breast cancers are the most common type of cancer in the UK¹, with around 15% of them classified as triple negative. TNBC presents a real unmet medical need in breast oncology². The disease is more common in younger people³ and black women for reasons that are only partially understood⁴. The disease is typically aggressive⁵, has fewer treatment options and a poor prognosis, although things are changing. We are now seeing more trials for new treatment options that hope to change how TNBC is treated in the future (olaparib, lenvatinib and pembrolizumab, durvalumab and capivasertib to name a few⁶).

Triple negative breast cancer definition

Triple negative breast cancers are defined by the lack of expression of oestrogen (ER), progesterone (PR) and the Human Epidermal Growth Factor 2 (HER2) receptors on tumour cells⁷. Specific targeted and hormonal therapies have been developed for ER+, PR+ and HER2+ breast cancers meaning there is a more efficient and specific treatment protocol for these cancers, however, as TNBC does not express either of the hormone receptors or the HER2 protein, patients with TNBC have not been able to benefit from these advancements.

Treating triple negative breast cancer can be challenging

As triple negative breast cancers do not express the main targets that are required for targeted treatment to be effective (i.e., oestrogen - ER, progesterone - PR and HER2), other more indiscriminate and traditional types of chemotherapy are then deployed. TNBC usually responds well to these conventional chemotherapies (such as doxorubicin or epirubicin⁸), but these types of therapies tend to have more complex toxicity profiles and are generally less well tolerated⁹ (more side effects). Another challenge is that although TNBC is sensitive to chemotherapy, early relapse is common. Investigations are taking place to challenge current treatment paradigms to improve outcomes for patients – but more work needs to be done.

The impact of COVID-19 on the treatment of cancer has been well documented. Important work will need to take place to understand the true extent of the impact, and what this means for patients.

Turning the tide on triple negative breast cancer

Immune checkpoint inhibitors (ICI) are now available to treat some patients with advanced TNBC who have programmed cell death ligand 1 (PD-L1) positive tumours¹⁰. TNBC is associated with high level of PD-L1 expression, which supports further investigation of ICI use within TNBC therapy11. An example of a PD-L1 targeted drugs is atezolizumab. Studies show that when treatments are used in combination, they have the potential to lead to improved survival in those patients with high-risk disease¹¹.

Furthermore, PARP (poly adenosine diphosphate-ribose polymerase) inhibitors (such as olaparib) have shown important activity in TNBC patients who have a germline BRCA (BReast CAncer gene) mutation¹². Around 5% of breast cancer patients are BRCA mutation carriers, and of those with the mutation, 57.1% have the TNBC subtype¹³. BRCA proteins play a role in repairing broken DNA. When mutations occur, broken DNA will not be repaired and cells may develop into cancer cells.

Identifying BRCA mutations is not straightforward because the gene is large and not all mutations indicate a real target for PARP inhibitor treatment. Research has therefore focused on identifying molecular signatures of BRCA mutation in patients’ breast cancer. This is done through tumour DNA analysis wherein a specific mutation footprint earmarks tumours for BRCA loss. Another avenue is through artificial intelligence interrogation of tumour sections which can also suggest which tumours carry BRCA mutations and are a target for PARP inhibitor treatment. Further clinical and translational data may identify more patients who could benefit from PARP inhibitors.

Arming the single arm trial or adding additional insight

IQVIA’s Oncology Insights Simulator (OIS) offers researchers the potential to look at many different aspects of TNBC treatment, by leveraging synthetic data¹⁴ from one of the most detailed cancer databases in the world, the National Cancer Registration database. Insights from these Real-World Evidence (RWE) studies go on to support clinical and economic evaluations, drive earlier patient access to novel products, and further the education of the scientific community on the effectiveness of medicines and pathways.

IQVIA and Genomics England have a long-standing collaboration and have been delivering a series of observational studies that were used to inform drug development¹⁵. This innovative platform can help to advance precision medicine and patients’ access to novel therapies, with the goal of delivering the right drugs to the right patients at the right time.

Regulators, payers, prescribers, and patients are recognising the benefit of utilising RWE – let us help you unlock the insights too

In order to accelerate approvals of the new and most promising treatments, regulators are increasingly being presented with single-arm efficacy data¹⁶. We see a trend towards better results when using external comparators with a Real-World Data component. This means that the data that is collected to establish Real-World Evidence is making a difference. See IQVIA’s white paper on making real-world evidence meaningful and actionable for more insight.

For more detailed and tailored information on how IQVIA can support you with Real World Evidence in improving outcomes for all cancer patients, contact Stephen Benson.

References

¹ Cancer Research UK, Breast Cancer statistics

² https://pubmed.ncbi.nlm.nih.gov/21161370/

³ Unique Challenges Facing Young Women With Breast Cancer, ASCO Post, May 25 2017 

⁴ Triple-Negative Breast Cancer Deadlier for Black Women, Partially Due to Lower Surgery, Chemotherapy Rates Breast Cancer.Org, May 18, 2021

⁵ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744285/

⁶ Cancer Research UK, Find a clinical trial

⁷ Cancer Research UK, Triple negative breast cancer

⁸ Macmillan Cancer Support, Research UK, Triple negative breast cancer

⁹ Toxicological aspects of antineoplastic drugs Doxorubicin and Epirubicin, Oat (Open access text)

¹⁰ National Cancer Institute, NCI Dictionaries, PD-L1

¹¹ https://pubmed.ncbi.nlm.nih.gov/32190733/

¹² https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682754/

¹³ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682754/

¹⁴ Unlocking the Potential of Real World Evidence for Oncology With Simulated Data, IQVIA blog post, 2019

¹⁵ IQVIA and Genomics England Launch the First Real-World Research Platform with Integrated Clinical and Genomic Data, IQVIA news article, 2018

¹⁶ Securing market access with single-arm trial data, IQVIA blog post, 2021