Early-stage lung cancer: Nivolumab improves 5-year survival rate

  • Researchers investigated the 5-year outcome of an immunotherapy drug on early-stage lung cancer.
  • 80% of those who took the immunotherapy drug survived after 5 years, whereas survival rates from standard treatments are 36–68%.
  • Further clinical trials are needed to confirm the results.

Lung cancer is the leading cause of cancer-related death globally. Around 80-85% of lung cancers are non-small cell lung cancers (NSCLC). These are a group of lung cancers that respond to similar treatments and have similar prognoses.

In recent years, treatments for advanced stages of NSCLC have improved. However, breakthroughs have only recently emerged for early-stage forms of the condition.

In a previous study, researchers found that 73% of patients who received two doses of the immunotherapy drug nivolumab before surgery were recurrence-free 18 months after surgery.

Knowing more about the long-term effects of nivolumab in NSCLC could improve treatment options and outcomes for patients.

Recently, the researchers conducted a 5-year follow-up of the patients in the previous nivolumab study. Those who received nivolumab had a decreased risk of recurrence after 5 years compared to standard treatment.

The study findings were published in Clinical Cancer Research.

What the researchers did 

For the study, the researchers recruited 21 patients with stage 1–3 NSCLC. Around half of the patients were female, and they were 67 years old on average.

Patients received two preoperative intravenous doses of nivolumab every 2 weeks. They also underwent surgery 4 weeks after their first dose.

One patient was not eligible for surgery due to the progression of their condition. Other patients were followed for an average of 63 months.

The researchers found that 60% of patients remained recurrence-free after 5 years. They also found that 80% were still alive after 5 years — significantly more than typical 5-year survival rates of 36- 68%.

The researchers noted that nivolumab treatment was linked to few side effects and did not lead to surgical delays.

“To our knowledge, this is the longest follow-up to date for a PD-1/ PD-L1 inhibitor in the neoadjuvant setting- before surgery- for any solid tumor,” says the senior author of the study, Dr. Patrick Forde, an associate professor of oncology at Johns Hopkins University.

How nivolumab works 

Nivolumab is an anti-programmed-cell death protein-1 (PD-1) therapy. PD-1 therapy works by blocking PD-1 proteins on cancer cells, which then allows immune T cells to kill cancer cells more effectively.

“I usually explain to the patient using the analogy that the drug removes the ‘cloak of invisibility’ of the cancer cells, so that T cells can ‘see’ them,” Dr. Chao Huang, associate professor of medical oncology at The University of Kansas Medical Center, not involved in the study, told Medical News Today.

Dr. Irina Sachelarie, board-certified hematologist and medical oncologist of MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, CA, not involved in the study, added that “[i]mmunotherapy has been proven to be very effective in the treatment of NSCLC, improving response rates, decreasing the rate of relapse, and improving survival.”

“We are presently using immunotherapy for the treatment of patients with metastatic NSCLC, but also for patients with early-stage NSCLC after surgery- adjuvant setting- or neoadjuvant setting,” she noted.

“Neoadjuvant therapy has potential advantages over adjuvant therapy, including early treatment of micrometastasis — cancer cells that have spread from the primary tumor to other parts of the body that are too few to be detected — increasing the rate of complete resection by decreasing the tumor burden before surgery, being able to assess response to treatment at the time of surgery, and better overall tolerability,” Dr. Sachelarie told us.

The researchers concluded that their findings suggest that treatment with nivolumab before surgery leads to better outcomes than standard treatment options.

Study limitations  

Dr. Pushan Jani, associate professor of pulmonology with McGovern Medical School at UTHealth Houston, not involved in the study, noted that the cohort size was too small to draw firm conclusions. He added that there is an unclear benefit for patients with stage 3 cancer.

He continued to explain that double-blind randomized phase 3 trials are needed to understand the treatment’s long-term effects in larger patient populations with more diverse kinds of resectable lung cancer.

Dr. Roy Herbst, chief of Medical Oncology and deputy director at Yale Cancer Center and Smilow Cancer Hospital, not involved in the study, agreed that randomized trials are needed to understand outcomes on patient survival.

I think we know that immunotherapy can shrink tumors before surgery, but not all tumors shrink,” he added. “This means we need to understand more about their ‘mechanisms of resistance’,” said Dr. Herbst.

“I [also] think we need to understand what more therapy patients need. Should we monitor patients with X-rays? Should we monitor them by looking in the blood for circulating tumor DNA? All of these are limitations and questions that will have to be figured out in the future.”

– Dr. Roy Herbst

Dr. Huang noted that while nivolumab is beneficial in the neoadjuvant setting, the current Food and Drug Administration (FDA)-approved standard neoadjuvant regimen for lung cancer — nivolumab and chemotherapy — may still be preferable.

“The study was initially published in the New England Journal of Medicine in 2018. Since then, another study — Checkmate 816 — a larger randomized phase 3 trial with 358 patients showed that the combination of nivolumab with chemotherapy was better than chemotherapy alone, with improved response, progression-free survival, and [overall survival]. The 4-year survival was also about 80%.”

Implications 

“This clinical study proves again the efficacy of immunotherapy in patients with NSCLC, particularly in the pre-operative setting. It shows that single-agent nivolumab provides excellent long-term outcomes at the cost of a low toxicity rate,” noted Dr. Sachelarie.

“Questions remain as to what subgroup of patients would benefit from the administration of nivolumab monotherapy rather than the chemo-immunotherapy combination,” she cautioned. “The authors hypothesize that perhaps the tumors with high PDL1 expression or those with earlier-stage (1 and 2) [cancer] could represent some of those subgroups.”

“Further studies — phase 3, larger studies, studies comparing immunotherapy alone vs chemo-immunotherapy — are needed. […] Until the results of those clinical trials become available, neoadjuvant monotherapy with nivolumab could be considered for tumors with high PD-L1 expression and those patients that do not desire to receive chemotherapy or have contraindications to chemotherapy,” Dr. Sachelarie argued.

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