Pre- and postsurgical immunotherapy may improve outcomes

By Staff 8 Min Read

  • Lung cancer is a major cause of all cancer-related deaths, with some treatment options involving surgery to remove cancerous cells from the lungs.
  • Researchers seek the best treatment options to provide the longest postsurgery survival times.
  • A recent study found that providing immunotherapy pre- and postsurgery helps improve survival rates compared to only receiving chemotherapy before surgery.

Lung cancer is the leading cause of cancer-related deaths in the world, but surgical interventions may improve survival rates, particularly when the disease is caught early.

One of the most common types of lung cancer is non-small cell carcinoma (NSCLC). A significant risk factor for this type of lung cancer is smoking. Treatment for NSCLC may involve cutting out parts of the lung to remove cancerous cells. After surgery, doctors may then have patients undergo chemotherapy or radiation to decrease the chances of lung cancer returning.

As with other forms of cancer, lung cancer treatment often involves a combined approach to help increase the chances of long-term survival.

Immunotherapy is a common treatment for lung cancer, and scientists are exploring the best ways to combine it with other therapy approaches. This form of targeted therapy uses monoclonal antibodies to help destroy cancer cells and prevent cancer growth.

A recent study published in The New England Journal of Medicineexamined the perioperative use of the immunotherapy treatment nivolumab among people who had resectable non-small-cell lung cancer. They compared the use of nivolumab pre and postsurgery with the use of only chemotherapy before surgery.

Participants who received nivolumab and chemotherapy before surgery and nivolumab postsurgery were more likely to be cancer-free 18 months later, and more participants in this group experienced a pathological complete response.

The study points to nivolumab’s usefulness in improving event-free survival in people with non-small-cell lung cancer (NSCLC).

This study was the international CheckMate 77T trial, a phase three, double-blind study. It included participants with operable non-small-cell lung cancer who had not received previous systemic anticancer treatment.

Researchers randomized 461 participants to receive either nivolumab or placebo. The intervention group received nivolumab and chemotherapy before surgery, while the control group received placebo and chemotherapy every three weeks for four cycles. In total, 229 were in the nivolumab group, and 232 were in the chemotherapy group.

Participants then underwent surgery within six weeks of this pre-surgical intervention. Within three months of surgery, the intervention group received nivolumab every four weeks for a year, while the other group received a placebo.

Researchers looked at event-free survival as a primary outcome. Secondary outcomes included:

  • A complete lack of viable tumor cells in the primary tumor location and sampled lymph nodes (pathological complete response) after surgery.
  • 10% or less viable cancer cells in primary tumor location and sampled lymph nodes (major pathological response) after surgery.
  • Overall safety and survival.

The average follow-up time with participants was 25.4 months.

Overall, the group that received nivolumab experienced superior outcomes to the chemotherapy group. Event-free survival at 18 months was 70.2% for the intervention group and 50% for the chemotherapy group.

“For patients with resectable stage IIA to IIIB non-small cell lung cancer (NSCLC), neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab had a significantly extended event-free survival compared with neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant placebo,” non-study author Mahran Shoukier, MD, an oncologist affiliated with Memorial Hermann, explained to Medical News Today.

Additionally, about a quarter of the intervention group also experienced a pathological complete response, while less than 5% of the chemotherapy group did.

About 35% of the intervention group experienced major pathological responses compared to about 12% of the chemotherapy group.

The groups experienced a similar number of adverse events, but the number of adverse events that resulted in treatment discontinuation was higher in the intervention group. Still, researchers noted that the intervention had no unexpected safety signals.

“The study showed the importance of using nivolumab in addition to the chemotherapy in the neoadjuvant regime for resectable NSCLC (stage IIA to stage IIIB) and then using nivolumab in the adjuvant setting after surgery. This will extend the event-free survival and increase the pathological response without unexpected safety signals.”

— Mahran Shoukier, MD, oncologist

The findings offer hope for improving survival rates for this deadly form of cancer.

“The burden imposed by lung cancer in the U.S. and the world at large is enormous,” Jack Jacoub, MD, board certified medical oncologist and medical director of MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, CA, told MNT. Jacoub was not involved in the study.

“Just a few years ago, the average survival for stage III lung cancer — [two-thirds] of the study population — was 1.5 years. Now, in the era of immunotherapy, this number has been dramatically improved,” Jacoub noted.

The study reported [that] 70% of patients are now alive and without any evidence of disease at that same time interval using perioperative therapy and 50% using preoperative therapy alone, which is tremendous progress. Moreover, the benefit from both approaches adds very little to the side effects already known with chemotherapy alone,” he continued.

Despite the promising implications, the study does have certain limitations.

First, it focused on a specific cancer type, meaning the results cannot necessarily be generalized to other cancer types. Less than 40% of participants completed one full year of nivolumab treatment post-surgery, which could have also impacted the results.

Researchers also acknowledge that Black participants were underrepresented, which suggests the need for more diverse follow-up. About 70% of the participants were male, so future research could include more female participants.

“Although we do not know overall survival — follow-up beyond the 2 years reported — it obviously will blow away the recent historical numbers with chemotherapy alone. Hence, this is a very significant trial and will likely change practice. This treatment will likely be available for stage II and III resectable lung cancer patients very soon in the U.S., and uptake by cancer treatment providers will likely be rapid thereafter.”

— Jack Jacoub, MD, board certified medical oncologist

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