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Combination Therapy for lung cancer: a game-changing treatment

Dr. Kenneth O’Byrne, Professor of Medical Oncology and Queensland Senior Clinical Research Fellow, presented the results of the Keynote-021 study combining immunotherapy and chemotherapy which showed high response rates that will greatly benefit patients with advanced non-small cell lung cancer

Nearly 2 million people are diagnosed with lung cancer (Globocan Project, World Health Organization),¹ with only 250,000 estimated to be alive five years later (Dr. Ted Hamilton, Florida Hospital Central Care). However, for this one of the top mortality-causing cancers, there is now a treatment that offers bigger hope: combination therapy.

Chemotherapy as a formerly available treatment

For decades, doctors have administered chemotherapy as the only available treatment for cancer patients. Dr. Kenneth O’Byrne, Professor of Medical Oncology and Queensland Senior Clinical Research Fellow, who has studied cancer for over 30 years has seen both positive and negative effects of chemotherapy.

Chemotherapy targets cancer cells but also kills healthy cells along the way.² Doctors acknowledge the fact that cancer cells can go undetected by the body’s immune system, thrive even under hostile environment, and manifest in its later stages.

Speaking at a PSMO symposium on the topic of “A New Standard-of-Care (SOC) for the treatment of First Line Advanced Non-Small Cell Lung Cancer (NSCLC)”, Dr. O’Byrne explained the ability of cancer cells to evade the immune system. This probably arises because tumors  are mutations and they develop the capacity to evolve, and as a natural selection  process, some tumor cells survive in hostile environment and this includes switching off processes in the immune system.

Lung cancer is just as evasive. Smoking, air pollution, asbestos, radiation, chromates and coke- oven emissions have been linked to lung cancer development.³ However, medical researchers have not come to one single cause of the disease.

Immunotherapy and a new glimmer of hope

Immunotherapy has held great promises in the treatment of lung cancer and other  malignancies. Patients receive drug treatment to activate the immune system and enable it to fight cancer. In some countries, including the Philippines, immunotherapy is used as first line treatment for lung cancer. Once the patient is diagnosed with cancer, there is no need to undergo chemotherapy as the patient can receive immunotherapy immediately.⁴ How can a breakthrough regimen like immunotherapy achieve this phenomenal result?

According to O’Byrne, scientific breakthroughs now allow doctors to identify which cancer cells switch off the immune system. The next step is to convert this discovery into a therapeutic agent.

The first of these “therapeutic agents” include pembrolizumab. Pembrolizumab interacts with PD-1 which is a checkpoint protein on immune cells called T-cells, to stop it from binding with PD-L1, which is a protein on some normal (and cancer) cells. Some cancer cells have large amounts of PD-L1, which helps them evade immune attack when bound with PD-1. In immunotherapy, this binding is prevented and immune response against cancer cells is boosted.⁴

An immunotherapy drug reactivates the patient’s immune response, fights cancer, and causes cancer cells to shrink. Observations show that the agent may be more effective as first line of treatment.⁴

Thus, early screening and diagnosis become a necessity in order to identify whether a particular lung cancer is due to a gene mutation or a protein proliferation, like the PD-L1. Dr. O’Byrne noted that clinical trials showed that immunotherapy as first line treatment yielded almost 20% survival rate.

Immunotherapy is already good news to cancer patients and their family. But, a more game- changing approach is getting medical attention.

Combination therapy changing the face of lung cancer treatment

Lung cancer patients are getting more benefits when they undergo a combination of immunotherapy and chemotherapy.4 Such approach is more capable of killing cancer cells and achieves remission, as clinical studies show.

The purpose of PD-L1 test is to enrich those patients who are likely to benefit from immunotherapy. With combined immunotherapy and chemotherapy, the response rate showed positive results.4 Combination therapy is especially suitable for patients with lower PD-L1 expression. O’Byrne cited the Immunotherapy in combination with chemotherapy trial which shows a response rate of around 50 percent and remission of 18 months4 – proving that the medical field has taken a massive step in lung cancer treatment compared to the old days of chemo.

Any kind of treatment will have side effects. It is important to remember that chemotherapy and immunotherapy express different toxicity profiles. When used in combination, O’Byrne emphasized the importance of patient education as well as a strong support team  which includes the patient’s medical team and family. ###

REFERENCES
  1. Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.
  2. Cancer Research UK. How chemotherapy works. https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/chemotherapy/how-chemotherapy-works. Reviewed November 15, 2017. Accessed December 19, 2018.
  3. Jenkins D. Synopsis of causation: lung cancer. UK Ministry of Defence. September 2008. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_dat a/file/384476/lung_cancer.pdf. Accessed December 21, 2018.
  4. Borghaei H. J Thorac Oncol. 2018. January 2019Volume 14, Issue 1, Pages 124–129 doi: 10.1016/j.jtho.2018.08.004. https://www.jto.org/article/S1556-0864(18)30942-0/fulltext