Perioperative Nivolumab Boosts EFS Versus Neoadjuvant-Only Nivolumab in NSCLC

There was a meaningful reduction in the risk for non-small cell lung cancer (NSCLC) recurrence or death in post-surgical patients treated with perioperative nivolumab (Opdivo) and chemotherapy versus only neoadjuvant nivolumab and chemotherapy, according to an analysis of two phase III trials.

The analysis showed an approximate 40% reduction in the risk of disease recurrence or death after surgery among patients who received at least one dose of adjuvant nivolumab following neoadjuvant nivolumab plus chemotherapy and surgery compared to those who did not receive adjuvant therapy, reported Patrick Forde, MD, of Johns Hopkins Medicine in Baltimore.

“In the near future we will not have a randomized trial available to us to try to make clinical decisions. And this analysis at present represents the only comparison of perioperative versus neoadjuvant-only immunotherapy treatments with resectable lung cancer,” explained Forde at the World Conference on Lung Cancer in San Diego. “With the caveat that this is an exploratory analysis, these results may help inform the potential benefit and our clinical decisions day-to-day when we see patients in the clinic after receiving neoadjuvant therapy and surgery for resectable lung cancer.”

Invited discussant Nan Wu, MD, of Peking University Cancer Hospital in Beijing, suggested that the comparison of patient-level data between the two trials — CheckMate 77T and CheckMate 816 — “supports perioperative nivolumab as a treatment option for eligible patients with resectable non-small cell lung cancer,” although he added that “phase III randomized clinical trials are needed for further validation.”

The current study compared event-free survival (EFS) from the time of surgery among patients in the CheckMate 77T trial, who received neoadjuvant nivolumab plus chemotherapy followed by definitive surgery and at least one dose of adjuvant nivolumab, with patients in CheckMate 816, who also received neoadjuvant nivolumab plus chemotherapy followed by definitive surgery but without adjuvant nivolumab.

CheckMate 816 demonstrated significant improvements in EFS with neoadjuvant nivolumab plus chemotherapy. At a follow-up of 29.5 months, median EFS was 31.6 months for patients receiving the nivolumab/chemotherapy combination versus 20.8 months for those who received chemotherapy alone (HR 0.63, 97.38% CI 0.43-0.91, P=0.005). As Forde pointed out, it is the sole FDA-approved neoadjuvant-only immunotherapy-containing regimen for resectable NSCLC.

CheckMate 77T built on this treatment regimen by demonstrating clinically meaningful improvements in EFS with perioperative nivolumab versus placebo (HR 0.58, 97.36% CI 0.42-0.81).

Forde and colleagues performed exploratory propensity score weighting analyses in order to reproduce a randomized trial by adjusting for baseline demographics and disease characteristics between the two study populations.

They found there was a substantial landmark EFS benefit with perioperative nivolumab EFS after propensity score weighing (HR 0.61, 95% CI 0.39-0.97) compared with neoadjuvant-only therapy.

A landmark EFS (unweighted) benefit was also observed regardless of clinical stage and pathological complete response (pCR) status:

• Stage IB to II: HR 0.53 (95% CI 0.25-1.11)
• Stage III: HR 0.63 (95% CI 0.37-1.07)
• With pCR: HR 0.58 (95% CI 0.14-2.40)
• Without pCR: HR 0.65 (95% CI 0.40-1.06)

EFS benefit was also observed with perioperative nivolumab in patients with PD-L1-negative tumors (HR 0.51, 95% CI 0.28-0.93), with an HR also trending in favor of perioperative therapy in patients with PD-L1-positive tumors (HR 0.86, 95% CI 0.44-1.79).

“However, we know that PD-L1-positive tumors tend to benefit from either neoadjuvant or perioperative or adjuvant therapy, so it’s quite possible we need longer follow-up in this group,” Forde observed.

The safety profiles of perioperative and neoadjuvant nivolumab were comparable, with similar rates of treatment discontinuation and surgery-related adverse events in both groups, Forde reported.

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