Immunotherapy before surgery improves survival in lung cancer

Results of a phase III clinical trial published in the New England Journal of Medicine show that five years after the end of treatment, lung cancer patients who received nivolumab immunotherapy along with standard chemotherapy before surgery had improved long-term survival compared to those who received chemotherapy alone.

Professor Patrick Forde from Trinity Saint James Cancer Institute (TSJCI), Trinity College Dublin Medical School presented the findings at the annual meeting of the American Society of Clinical Oncology in Chicago.

Professor Forde led the CheckMate 816 study, which enrolled 358 patients from around the world who were diagnosed with the most common type of lung cancer, non-small cell lung cancer (NSCLC), at a stage where it could be removed with surgery. However, despite surgery, >50% of patients with stage 2 or 3 lung cancer eventually relapse.

Immunotherapy drugs known as immune checkpoint inhibitors, particularly those that block the PD-1 receptor, have led to improved survival in patients with advanced cancer by causing the patient’s immune system to stop recognizing the tumor. However, no study to date has shown a long-term benefit of such treatments for curing early-stage lung cancer.

Previously working as an oncologist at Johns Hopkins Hospital in the US, Prof. Forde led the first clinical trial on the use of immunotherapy before surgery (“neoadjuvant therapy”) for lung cancer, the results of which were published in the New England Journal of Medicine in 2018. That study found that among 20 patients who underwent surgery after two doses of immunotherapy, nearly half had little or no cancer at the time of surgery.

An earlier report on the CheckMate 816 study reported that lung cancer patients who received immunotherapy along with chemotherapy before surgery were more likely to have their cancer completely eradicated by the time of surgery, and they also had lower rates of cancer recurrence. Side effects did not increase when immunotherapy was added, and overall the surgeries went well.

These results have led to the approval of neoadjuvant nivolumab therapy in combination with chemotherapy in several countries around the world, including as standard treatment for eligible patients in Ireland.

Patients who received immunotherapy plus chemotherapy before surgery were about 10% more likely to be alive after five years than those who received chemotherapy alone, according to the latest study data. Among the 24% of patients receiving immunotherapy and chemotherapy who had no signs of cancer left by the time of surgery, which is called a complete pathomorphologic response, no patient had died of lung cancer five years later.

Prof. Forde is also co-leading an international clinical trial being conducted in Ireland at TSJCI, Beaumont, Galway and Mater hospitals to further improve outcomes for patients who have undergone surgery. Results from part of this study have also been published in Nature Medicine.

In the NeoCOAST-2 study, patients who received standard chemoimmunotherapy plus a new treatment called antibody-drug conjugate before surgery were more likely to have no remaining viable cancer at the time of surgery, suggesting that this additional treatment could further improve outcomes.

Professor Forde said: “Immunotherapy has helped many patients with stage 4 lung cancer to live longer and with a good quality of life. Until recently, we had no new treatments that could improve the chances of a cure after lung cancer surgery.”

Using immunotherapy along with chemotherapy before lung cancer surgery has now been shown to reduce the risk of cancer recurrence and improve long-term survival. Oncology clinical trials play a key role in improving outcomes for patients with cancer and provide early access to the latest advanced cancer treatments.