Perioperative nivolumab plus chemotherapy improves outcomes in stage III NSCLC
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Key takeaways:
- A greater proportion of patients who received the regimen vs. chemotherapy alone had a pathologic complete response.
- No patients with a pathologic complete response experienced relapse at 2 years of follow-up.
More than one-third of adults with previously untreated stage III non-small cell lung cancer exhibited a pathologic complete response after receiving perioperative nivolumab plus chemotherapy, results of a randomized phase 2 trial showed.
The immuno-chemotherapy combination also produced significantly higher 2-year OS and PFS rates than chemotherapy alone prior to surgery, according to data published in The New England Journal of Medicine.
“We were the first to commit to this strategy, which has been followed by [many in] the pharmaceutical industry,” Mariano Provencio, MD, PhD, head of the medical oncology department at Puerta de Hierro University Hospital, Autonomous University of Madrid, told Healio. “It is easy to administer, commonly used in [patients with metastatic disease] and inexpensive.”
Background
Approximately one-fifth of individuals diagnosed with NSCLC have stage III disease, according to Provencio.
Unfortunately, he added, there is no consensus on what the standard treatment should be for this subset of patients.
“We had initiated a neoadjuvant research line in locally advanced lung cancer and were convinced that we could change the standard of treatment in these patients,” he said.
Methodology
The multicenter, open-label NADIM II trial sought to determine the safety and efficacy of neoadjuvant nivolumab (Opdivo, Bristol Myers Squibb) plus platinum-based chemotherapy followed by adjuvant nivolumab vs. neoadjuvant chemotherapy alone for locally advanced NSCLC.
The researchers randomly assigned 86 adults with resectable stage IIIA or IIIB NSCLC in a 2:1 ratio to receive either the nivolumab-chemotherapy regimen (experimental group; n = 57) or chemotherapy alone (control group; n = 29) before surgery. Those in the experimental group who had microscopically margin-negative resections received adjuvant nivolumab for 6 months.
Pathologic complete response — defined as absence of viable tumor cells in the primary tumor site and surgically removed lymph nodes — determined by blinded independent central review served as the study’s primary endpoint.
Secondary endpoints included PFS and OS at 2 years and safety.
Median follow-up was 26.1 months (interquartile range, 17.4-30.9), with researchers reporting 95.2% data maturity at 24 months.
Key findings
Researchers reported a 37% (95% CI, 24-51) pathologic complete response rate for the experimental group compared with 7% (95% CI, 1-23) for the control group (RR = 5.34; 95% CI, 1.34-21.23).
Ninety-three percent of patients in the experimental group underwent subsequent surgery compared with 69% in the control group (RR = 1.35; 95% CI, 1.05-1.74).
Kaplan-Meier estimates showed 24-month PFS rates of 67.2% for the experimental group and 40.9% for the control group (HR for disease progression, disease recurrence or death = 0.47; 95% CI, 0.25-0.88).
Likewise, 24-month OS estimates favored the experimental group (85% vs. 63.6%; HR for death = 0.43; 95% CI, 0.19-0.98).
Nineteen percent of patents in the experimental group experienced grade 3 or grade 4 treatment-related adverse events compared with 10% in the control group.
Adverse events led to discontinuation of treatment for five patients, including four in the experimental group and one in the control group.
Investigators noted no delays in surgery due to treatment-related adverse events.
Clinical implications
The results demonstrate that neoadjuvant nivolumab plus platinum-based chemotherapy can significantly improve OS and pathologic complete response rates compared with chemotherapy alone, according to Provencio.
“We are able to operate and obtain these results in an important group of patients who were previously considered unresectable,” he told Healio.
Further study should seek to optimize neoadjuvant therapy by determining which patients are most likely to benefit from the addition of nivolumab, he added.
For more information:
Mariano Provencio, MD, PhD, can be reached at Medical Oncology Department, Hospital Universitario Puerta de Hierro–Majadahonda, Calle Manuel de Falla 1, 28222 Majadahonda, Madrid, Spain; email: mprovenciop@gmail.com.
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