Monotherapy treatment with neoadjuvant nivolumab (Opdivo; Bristol Myers Squibb), an anti–PD-1 immune checkpoint blockade, showed an 80% increase in 5-year overall survival (OS) in patients with advanced non–small cell lung cancer (NSCLC), according to investigators at Johns Hopkins University and Memorial Sloan Kettering Cancer Center. Investigators published findings of the open-label, single-arm, phase 1b/2 study (NCT02259621) that evaluated 2 doses of nivolumab for resectable NSCLC in Clinical Cancer Research.1
Lung cancer illustration | Image credit: SciePro - stock.adobe.com
“The results from the 5-year followup analysis indicate that neoadjuvant nivolumab was safe in long-term followup and led to encouraging survival in this patient cohort,” study author Patrick Forde, MBBCh, an associate professor of oncology and a codirector of the Division of Upper Aerodigestive Malignancies at Johns Hopkins in Baltimore, Maryland, said in a press release. “The long-term safety and efficacy data from this study provide further support for the use of nivolumab in the neoadjuvant setting.”2
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Primary end points were safety and feasibility, and designated secondary end points included pathologic markers of response as measured by percentage of residual viable tumor (%RVT). The measurement of %RVT could be either a pathologic complete response (pCR) of 0% RVT or a major pathologic response (MPR) with an RVT of 10% or less. Other key secondary end points were recurrence-free survival (RFS) and OS (measured from date of surgery).1
The study enrolled 21 patients (20 of whom underwent surgery) aged 18 years and older with stage I to stage IIIA resectable NSCLC. During the trial, patients received 2 preoperative doses of intravenous nivolumab (3 mg/kg) every 2 weeks, then underwent definitive resection 4 weeks after dose 1.1
Investigators noted that they found neoadjuvant nivolumab feasible, safe, and effective after the trial. At followup (63 months), RFS was 60% among patients who received nivolumab before resection. Their rates of pCR and MPT were 10% and 45%, respectively.1
“To our knowledge, this is the longest follow-up to date for a PD-1/PD-L1 inhibitor in the neoadjuvant setting for any solid tumor,” Forde said in the press release.2
Among patients with MPR, 89% were alive and cancer free at 5 years. Additionally, neoadjuvant treatment was associated with very few severe adverse events (AEs); only 1 patient experienced a late-onset grade 3 immune-related dermatologic AE, which was successfully managed. Neoadjuvant treatment did not delay patient surgeries.1
During a subgroup analysis, investigators observed a positive link between RFS and MPR; 1 patient with MPR experienced recurrence vs 6 patients without MPR. Investigators have yet to find the best treatment for patients with suboptimal pathologic response (ie, adjuvant chemotherapy).1
Patients with stages I or II NSCLC had more favorable RFS outcomes than those with stage 3A NSCLC, according to investigators. Furthermore, the %RVT may increase as tumor stage increases, and a patient may come to be at greater risk of recurrence. In total, 7 recurrences occurred in the 20-patient cohort, 4 of which occurred after more than 1 year post surgery. Most of these patients benefited from additional definitive local therapy.1
In addition, at least 66% of patients without MPR after nivolumab had a PD-L1–negative form of the disease. Conversely, the team observed that patients with PD-L1–positive tumors showed more favorable RFS outcomes after 5 years. These findings are supported by results from the previous CheckMate 816 study (NCT02998528), in which investigators observed an association between reduced pathologic response and pretreated PD-L1–positive tumor.1
The study was primarily limited by its small cohort size, making it difficult to assess the significance of the link between subgroups and long-term clinical outcomes.
In 2022, the FDA approved neoadjuvant nivolumab with platinum-doublet chemotherapy for stage I through stage IIIA NSCLC based on the results of CheckMate 816, which also proved the prognostic value of MPR and RFS. New trials are assessing myriad nivolumab immunotherapeutic combinations.1
“Further studies will help us determine whether select patients may benefit from immunotherapy alone,” Forde stated.2
1. Rosner S, Reuss JE, Zahurak M, et al. Five-year clinical outcomes after neoadjuvant nivolumab in resectable non–small cell lung cancer. Clin Cancer Res. 2023;29(4):705-710. doi:10.1158/1078-0432.CCR-22-2994
2. Neoadjuvant nivolumab shows long-term benefit in patients with non-small cell lung cancer. News Release. American Association for Cancer Research. February 15, 2023. Accessed March 6, 2023. https://www.aacr.org/about-the-aacr/newsroom/news-releases/neoadjuvant-nivolumab-shows-long-term-benefit-in-patients-with-non-small-cell-lung-cancer/