Nivolumab improves survival for patients with early‑stage non‑small cell lung cancer, according to a five‑year follow‑up of a small neoadjuvant trial. The report shows that 80% of participants were alive at five years, compared with historic rates of 36–68% for standard care.
Trial design and outcomes
The study enrolled 21 adults with stage 1–3 disease, half of them women, with an average age of 67. Each received two pre‑operative intravenous doses of the drug every two weeks, followed by surgery four weeks after the first infusion.
One patient could not undergo resection because the cancer progressed before surgery. The remaining participants were monitored for a median of 63 months.
Most patients survived five years.
Sixty percent showed no disease recurrence, a level far above typical ranges for similar cases.
Adverse events were limited, and no delays in operative scheduling were attributed to the treatment.
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Expert observations
“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,” said senior author Dr. Patrick Forde, associate professor of oncology at Johns Hopkins University.
“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,” explained Dr. Chao Huang, associate professor of medical oncology at the University of Kansas Medical Center.
Dr. Irina Sachelarie, a board‑certified hematologist‑oncologist, noted that immunotherapy has been proven to be very effective in the treatment of NSCLC.
She added that both adjuvant and neoadjuvant settings are now using such approaches.
Independent researchers cautioned that the cohort is small.
The sample size limits firm conclusions, especially for stage 3 disease.
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“We need randomized phase 3 data to clarify long‑term benefits and to identify mechanisms of resistance,” said Dr. Roy Herbst, chief of medical oncology at Yale Cancer Center.
Given the limited data, the drug will likely be evaluated in larger, multi‑center trials that compare it directly with standard chemotherapy regimens.
Clinicians could have a low‑toxicity option for patients who cannot tolerate chemotherapy.
The FDA currently approves a combination of the same PD‑1 inhibitor with chemotherapy for neoadjuvant use. A larger phase 3 trial, CheckMate 816, reported four‑year survival close to the rate seen in the small study, suggesting that adding chemotherapy may boost outcomes further.
CheckMate 816 involved 358 participants and showed improved response rates, progression‑free survival, and overall survival compared with chemotherapy alone.
Researchers plan to initiate additional studies that will explore monotherapy versus chemo‑immunotherapy, as well as biomarkers such as PD‑L1 expression that might predict benefit.