Neoadjuvant nivolumab confers durable survival benefit in resectable NSCLC
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Treatment with neoadjuvant nivolumab led to higher 5-year survival rates compared with historical data among patients with resectable non-small cell lung cancer, according to study results published in Clinical Cancer Research.
Researchers also reported few adverse effects, with only one late-onset immune-related adverse event, and no surgical delays that resulted from treatment.
Rationale and methodology
“We conducted this investigator-initiated clinical trial with the goal of elucidating mechanisms of response and resistance to anti-PD-1 immunotherapy in early-stage lung cancer,” Patrick M. Forde, MBBCh, co-director of the division of upper aerodigestive malignancies at Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University, told Healio. “Delivering nivolumab [Opdivo, Bristol Myers Squibb] prior to surgery allows for the lung cancer removed at surgery to be studied in depth, as well as assessment of the pathologic response in the tumor as a potential marker of efficacy.”
The phase 1b/phase 2 trial included 21 patients (median age at enrollment, 67 years: 52% women) with stage I to stage IIIA NSCLC. Patients received 3 mg/kg nivolumab every 2 weeks for 4 weeks before surgery.
Safety and feasibility, which had been reported previously, served as the primary endpoints. The current analysis included 5-year rates of recurrence-free survival and OS and associations with major pathologic response and PD-L1 among the 20 patients who underwent resection.
Median follow-up was 63 months.
“[This represents], to our knowledge, the longest follow-up data available after neoadjuvant anti–PD-1 therapy in any cancer type,” researchers wrote.
Findings
Results showed a 5-year recurrence-free survival rate of 60% and 5-year OS rate of 80%. This exceeded the historical 5-year survival rates of 36% to 68% for this patient population, according to researchers.
In addition, researchers observed a trend toward favorable recurrence-free survival for both major pathologic response (HR = 0.61; 95% CI, 0.15-2.44) and pretreatment tumor PD-L1 positivity (HR = 0.36; 95% CI, 0.07-1.85).
Researchers reported a 5-year DFS rate of 89% among patients with major pathologic response and no cancer-associated deaths among those patients. However, six patients without major pathologic response experienced tumor relapse, and three of them died.
“We have now followed patients for 5 years and discovered that the treatment is safe in the long-term and patients who had a major pathologic response did very well,” Forde said. “This lends further weight to the concept of using pathologic response after neoadjuvant immunotherapy for lung cancer as a potential early predictor of benefit.”
Study limitations included the small study population and single-arm design, researchers noted.
Implications
“Since this trial was developed, neoadjuvant chemotherapy plus nivolumab has become a standard of care for lung cancer based on the CheckMate 816 trial that showed increased pathologic response and event-free survival compared with chemotherapy alone,” Forde said. “Future studies are now examining whether the addition of novel agents to chemoimmunotherapy may increase pathologic responses further and ultimately improve survival for patients with early-stage lung cancer.”
References:
- Neoadjuvant nivolumab shows long-term benefit in patients with non-small cell lung cancer (press release). Published Feb. 15, 2023. Accessed Feb. 15, 2023.
- Rosner S, et al. Clin Cancer Res. 2023;doi:10.1158/1078-0432.CCR-22-2994.
For more information:
Patrick M. Forde, MBBCh, can be reached at pforde1@jhmi.edu.
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Rosner S, et al. Clin Cancer Res. 2023;doi:10.1158/1078-0432.CCR-22-2994.
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