- Cancer death rates have declined significantly over the past 20 years according to the
Centres for Disease Control and Prevention(CDC), yet some types of cancer remain difficult to treat.
- Lung cancer is the
third most common cancer, and it has the highest death rate in the United States.
- Using immunotherapy alongside chemotherapy has proved promising in a recent phase 3, multicenter, clinical trial of patients with non-small cell lung cancer that has spread.
- Following the publication of the trial results, the Food and Drug Administration (FDA) has approved AstraZeneca’s drugs Imfinzi (durvalumab) and Imjudo (tremelimumab) alongside chemotherapy already approved in the U.S. for patients with metastatic non-small cell lung cancer.
Lung cancers are the third most common form of cancer in the US, and they have the highest rate of death, according to the
Lung cancers are generally divided into two types, small cell lung cancer (SCLC), which affects nearly 20% of total patients, and non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancer cases.
While both do have relatively high death rates, death rates for the disease overall have declined by 56% since 1990 in men and 32% since 2002 in women. The 5-year survival rate for NSCLC is 26%, compared to 7% for SCLC.
Many cancer treatment improvements over the past decade are due to an increasing understanding of cancer genomics, and the introduction of increasingly personalized treatment plans that target the specific mutations that an individual cancer exhibits.
However, there have been few options for people with NSCLC that has spread to distant sides of the body, called metastatic NSCLC.
Dr. Wael Harb, hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, CA, told Medical News Today in an email that “lung cancer is the leading cause of cancer-related mortality in the United States and worldwide,” with “more than 80% of lung cancers […] classified as NSCLC.”
“NSCLC is hard to treat since it is often diagnosed at advanced stage that is not amenable to curative surgery or definitive chemo-radiation. Some of these patients treated with surgery or radiation relapse and others are diagnosed with advanced or metastatic NSCLC, which is treatable but not curable with current available treatment options.”
– Dr. Wael Harb
One option which could prove promising for treating these cancers is
Immunotherapies work by boosting the immune system’s ability to target and destroy cancer cells. These can work in a variety of ways, either by increasing the number of cells that are produced by the immune system that can kill cancer cells, or by stopping the mechanisms that can kill immune cells.
Dr. Alastair Greystoke is an oncologist at Newcastle’s Northern Centre for Cancer Care in the United Kingdom, specializing in lung cancer, and he is also the joint chief investigator of the CONCORDE trial in the U.K., which looks at the effect of different drugs in combination with radiotherapy on lung cancer.
He told MNT that: “One of the roles of the immune system is to kill cancer cells in the first place […] With immune therapy we are asking the cells to do what they should already be doing which is killing the cancer cells.”
He explained that this differed from chemotherapy, and cancer cells can learn to repair the damage the chemotherapy does to its DNA. Using immunotherapies alongside chemotherapy provided a different target.
The drug durvalumab is an existing immunotherapy used for NSCLC, which seeks out cancer cells by looking for a specific protein called the PD-L1 protein and attaching it. The immune system then recognizes the marked cells as cancer cells and kills them.
Both received approval from the FDA for the treatment of advanced liver cancer in October 2022, following the publication of the results of the HIMALAYA phase 3 trial.
However, results from trials using immunotherapies that target both of these pathways in NSCLC have so far been mixed.
The recent publication of results from the POSEIDON III trial, which looked at the use of these two immunotherapies alongside a platinum-based chemotherapy in people with NSCLC have led to the FDA approving a new treatment regime.
With results published in the Journal of Clinical Oncology, the POSEIDON III trial included a cohort of 1,013 patients from 142 sites in 18 countries, who had metastasized NSCLC for which they had received no other drug-based treatment.
For the randomized control trial they were split equally into three treatment groups:
- one group received both tremelimumab plus durvalumab alongside a platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until their cancer progressed and one additional tremelimumab dose
- another group received durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until their cancer progressed
- the final group received chemotherapy for up to six 21-day cycles.
Researchers found that patients on durvalumab plus chemotherapy had a 26% higher chance of survival without cancer progression than those on just chemotherapy, but there was no difference in overall survival rate.
They also found that those on tremelimumab plus durvalumab plus chemotherapy were 28% more likely to survive with no progress of the cancer, and had a 22% overall higher survival rate.
The rate of adverse treatment side effects was higher when the immunotherapies were used, with 52% of participants on both immunotherapies and chemotherapy reporting adverse, treatment-related events, compared to 44% on just chemotherapy.
The number of people who stopped treatment due to adverse treatment-related side effects of 16% compared to 10% for people on just chemotherapy.
Dr. Harb noted that the trial had shown the use of the immunotherapies alongside chemotherapy was more than 25% effective than using chemotherapy alone, but noted the regimes tested had been limited and there were significant side effects reported.
He told MNT: “Since we have several approved options of combination of immunotherapy and chemotherapy, it is not clear how this compares to other regimens such as Keytruda and chemotherapy. Potential added toxicity and increased costs for this treatment regimen need to be taken into consideration.”
“The treating oncologist will need to understand in which patient population this regimen might have an advantage over other approved combination regimens of immunotherapy and chemotherapy,” he cautioned.