Neoadjuvant nivolumab offers sustained efficacy in resected NSCLC

Treatment with neoadjuvant nivolumab (Opdivo) improves 5-year recurrence-free survival (RFS) and overall survival compared with historical outcomes in patients with surgically resected non-small cell lung cancer (NSCLC), according to It led to promoting the OS rate (OS) rate. Final Analysis of Phase 1b/2 Study (NCT02259621).

With a median follow-up of 63 months, 60% (n = 12) of the 20 patients undergoing surgical resection after neoadjuvant nivolumab in this trial were relapse-free after 5 years, Both patients, with 80% (n = 16) having a complete pathologic response (pCR) after neoadjuvant nivolumab, were alive and disease-free at 5 years.¹

“The results of this long-term follow-up analysis show favorable clinical outcomes after only two doses of the neoadjuvant nivolumab before resection, highlighting the persistence of this drug in the perioperative period,” said Johns Hopkins Sidney. Kimmel Cancer’s Samuel Rosner, MD Baltimore, Maryland center on live^®.

In 2018, Patrick M. Forde, MBBCh, and colleagues at Johns Hopkins Sidney Kimmel Cancer Center presented early data from this Phase 1/2 trial. type. This trial shows that this treatment is safe and feasible, with 45% (95% CI, 23%-68%) of patients achieving a major pathologic response (MPR) and tumor His pCR was obtained in 10% of his patients who had a complete resection of his. Side effects (AEs) are rare, regardless of PD-L1 status.² The 5-year clinical results of this trial represent the longest follow-up data for a neoadjuvant PD-1 inhibitor in any type of cancer.¹

The trial enrolled patients aged 18 years and older with resectable stage I-IIIA NSCLC. A total of 21 patients received two doses of 3 mg/kg nivolumab four weeks before planned surgery. One patient was subsequently declared inoperable due to progression of the primary disease and died of cancer within 9 months of enrollment.

A total of 6 patients received standard of care adjuvant therapy in the form of 3 to 4 cycles of cisplatin-based chemotherapy per study protocol. No patients received adjuvant radiotherapy or targeted therapy.

The primary endpoints of this trial were the safety and feasibility of the neoadjuvant nivolumab. previously reportedThis updated analysis describes the 5-year outcomes of all patients with successfully radically resected NSCLC after study treatment. Primary exploratory endpoints were pathologic markers of response, including pCR, defined as 0% residual viable tumor, and MPR, defined as ≤10% residual viable tumor. RFS, measured from the date of surgery. OS, measured from the date of surgery.

The median patient age was 67 years (range, 55–84 years). Regarding clinical stage at diagnosis, 22% (n = 2), 56% (n = 5), and 22% (n = 2) of MPR patients had stage I, II, or IIIA disease. 18% (n = 2) ), 45% (n = 5) and 36% (n = 4) of patients without MPR. In patients with and without MPR, 33% (n = 3) and 36% (n = 4) had PD-L1 status of at least 1%, 22% (n = 2) and 55% (n = 6), respectively had a Less than 1% had PD-L1 status, and 44% (n = 4) and 9% (n = 1) had non-evaluable PD-L1 status.

“Exploratory subgroup analyzes suggest patients with MPR and pCR after the neoadjuvant nivolumab showed excellent clinical outcomes,” said Dr. Rosner. After treatment she developed her MPR in 9 patients and he was 89% (n = 8) alive and disease-free at 5 years follow-up.

In the 5-year analysis, MPR and PD-L1 positivity in pretreatment tumors trended toward improved RFS, with HRs of 0.61 (95% CI, 0.15-2.44) and 0.36 (95% CI, 0.07-1.85), respectively. was.

Of the 7 disease recurrences observed, 86% (n = 6) occurred in patients without MPR after neoadjuvant nivolumab. Of the six patients with recurrent disease and for whom her pretreatment PD-L1 assessment was available, four were her PD-L1 negative.

Patients with stage I/II NSCLC had a numerically better RFS compared with stage IIIA patients (HR, 0.42; 95% CI, 0.11-1.62).

An exploratory analysis assessing another pathologic response threshold of 50% of residual viable tumor, or partial pathologic response, showed a favorable RFS association (HR, 0.36; 95% CI, 0.09-1.51). When assessed as a continuous variable, increasing percentages of residual viable tumor tended to increase risk of recurrence (HR, 2.9; 95% CI, 0.51-16.57).

In 11 patients with tumor samples available for sequencing analysis, mean tumor mutational burden was not associated with improvement in RFS or OS when evaluated as a continuous variable, with a respective HR of 1.0 (95% CI, 0.99 -1.01) and 1.01 (95% CI, 1.00-1.02).

Seven tumor recurrences occurred during the observation period, of which 57% (n = 4) occurred more than 1 year after surgery. Three patients experienced intrathoracic recurrence. Of her 7 total patients who relapsed, 4 were still alive 5 years after treatment for her NSCLC recurrence, 3 of whom had final local disease for metachronous oligometastatic disease. The treatment was successful.

As previously reported, treatment with the adjuvant nivolumab induced few AEs and did not delay surgery. One patient experienced dermatitis herpetiformis with alopecia universalis, a late-onset grade 3 cutaneous immune-related AE, 16 months after her last dose of nivolumab. This AE was successfully managed by immunosuppression. The investigators did not observe any other late-onset immune-related AEs.

No cancer-related deaths occurred in MPR patients. However, her one patient with MPR without NSCLC recurrence died at 2 months after she died of secondary effects from a traumatic head injury. Of her 11 patients without MPR, 6 had tumor recurrence and 3 died.

“While this analysis is certainly limited by the small cohort size and overall low recurrence rate, it nonetheless supports the growing role of immune checkpoint inhibitors in the preoperative treatment of early-stage NSCLC. We are awaiting long-term follow-up from pivotal studies such as a large prospective study in this setting, further enhancing our findings and highlighting additional biomarkers of response to other therapeutic modalities. but [phase 3] CheckMate-816 Trial [NCT02998528]long-term follow-up from such pilot studies may offer a glimpse into the future of this rapidly evolving therapeutic landscape.

References

1. Rosner S, Reuss JE, Zahurak M, et al. His 5-year clinical outcome after his administration of neoadjuvant nivolumab in resectable non-small cell lung cancer. Clinical cancer research. 2023;29:705-710. doi:10.1158/1078-0432.CCR-22-2994
2. Forde PM, Chaft JE, Smith KN et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med2018;378(21):1976-1986.doi:10.1056/NEJMoa1716078