Nivolumab-chemo poised to alter NSCLC treatment landscape

In the 3-year analysis of the phase III CheckMate 816 trial, neoadjuvant nivolumab plus platinum doublet chemotherapy (nivo-chemo) continued to provide durable benefit for individuals with resectable non-small-cell lung cancer (NSCLC).

After a median follow-up of 41.4 months, nivo-chemo reduced the risk of disease recurrence, progression, or death by 32 percent (hazard ratio [HR], 0.68), demonstrating a 3-year event-free survival (EFS) rate of 57 percent vs 43 percent with chemo alone. [ELCC 2023, abstract 84O]

“Median EFS was not reached with nivo-chemo. With chemo alone, it was 21.1 months,” said investigator Dr Nicolas Girard from Institut du Thorax Curie-Montsouris, Institut Curie, Paris, France, at ELCC 2023. The 3-year PFS favoured nivo-chemo over chemo alone across most subgroups.

The EFS benefit of nivo-chemo was seen regardless of surgical approach (HR, 0.61 [minimally invasive] and HR, 0.74 [thoracotomy or conversion]) or extent of resection (HR, 0.62 [lobectomy] and HR, NC* [pneumonectomy]). EFS rates with nivo-chemo in these subgroups ranged between 61 and 67 percent, whereas with chemo alone, rates were lower (between 48 and 53 percent).

“In patients with R0 resection, which is the goal of surgery in this setting, 3-year EFS rates were 64 percent vs 51 percent for nivo-chemo vs chemo, respectively (HR, 0.65),” said Girard.

There was also a benefit with nivo-chemo vs chemo alone in terms of TTDM** (HR, 0.55) and post-surgical recurrence rate (28 percent vs 42 percent).

 

Biomarker analysis

Nivo-chemo recipients with pathologic complete response or major pathologic response (PR) had higher four-gene*** inflammatory signature (IS) scores. “This was not observed in the control arm because of the limited number of PR after chemo alone,” said Girard.

Nivo-chemo improved EFS among those with high vs low four-gene IS score (70 percent vs 55 percent). Again, this was not seen with chemo alone. This result aligns with evidence reflecting a correlation between high inflammatory score and higher response rate or improved survival, Girard noted.

 

OS, safety

There was a trend toward longer overall survival (OS) with nivo-chemo vs chemo alone, but the boundary for statistical significance has not been crossed (HR, 0.62; p=0.012). Despite the need for more mature data, these findings are encouraging, said Girard.

“[Moreover,] we did not identify any additional signal of toxicity. The addition of nivolumab to chemo was not associated with increased toxicity or surgical complications,” he continued.

Grade 3/4 treatment-related adverse event (TRAE) rates for nivo-chemo and chemo alone were similar (36 percent and 38 percent). Immune-mediated AEs^# tied to nivo-chemo were infrequent (between 3 and 8 percent) and mild in severity.

 

A ray of hope for NSCLC patients

This study randomized 358 participants 1:1 to three cycles of chemo Q3W with or without nivolumab 360 mg. Surgery was to be performed 6 weeks after the last neoadjuvant treatment dose. Optional adjuvant therapies could be administered at investigator’s discretion.

“These updated results are immensely important, as they show the addition of nivolumab to chemo provides sustained efficacy over 3 years when given before surgery and provide hope for the large portion of NSCLC patients facing high recurrence rates and for whom cure is not feasible with surgery alone,” Girard noted in a press release.

“As the first positive phase III trial with an immunotherapy-based combination in the neoadjuvant setting, [the findings] contribute valuable knowledge to the scientific community studying resectable NSCLC,” he continued. “With long-term data showing the combination [may help] prevent disease recurrence and progression for different types of patients, alongside an encouraging trend of longer OS, this regimen is poised to change the way nonmetastatic NSCLC is treated.”