Publication

Article

Supplements and Featured Publications
The Current and Future State of Immune Checkpoint Inhibitors in NSCLC
Volume 01
Issue 01

Nivolumab/Ipilimumab Demonstrated Long-term Efficacy in Metastatic NSCLC

Author(s):

Results of a 5-year analysis of the phase 3 CheckMate 227 trial showed that the combination of nivolumab plus ipilimumab elicited durable overall survival benefit in patients with metastatic non–small cell lung cancer regardless of PD-L1 expression compared with chemotherapy.

Julie R. Brahmer, MD

Julie R. Brahmer, MD

Results of a 5-year analysis of the phase 3 CheckMate 227 trial (NCT02477826) showed that the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) elicited durable overall survival (OS) benefit in patients with metastatic non–small cell lung cancer (NSCLC) regardless of PD-L1 expression compared with chemotherapy. Updated data were presented at the 2022 ASCO Annual Meeting.1

The 5-year rate of overall survival (OS) rate with the immunotherapy combination among those with PD-L1 expression of at least 1% (n = 396) was 24% vs 14% with chemotherapy alone (397). Among those with PD-L1 expression of less than 1%, the 5-year OS rate was 19% for those who received the combination (n = 187) vs 7% among patients who received chemotherapy (n = 186).

The immunotherapy combination also had a significantly higher duration of response (DOR) vs chemotherapy. Among patients with PD-L1 expression of at least 1%, the median DOR with the combination was 24.5 months vs 6.7 months with chemotherapy. For those with PD-L1 expression less than 1% the median DOR was 19.4 vs 4.8 months, respectively.

“Nivolumab and ipilimumab led to increased 5-year survivorship among these 5-year survivors and regardless of PD-L1 expression level,” Julie R. Brahmer, MD, director of the thoracic oncology program and professor of oncology at Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, said in her presentation. “Responses were maintained for greater than 5 years in over 40% of those who responded.”

The phase 3 CheckMate 227 stratified patients with stage IV or recurrent NSCLC who had no prior systemic therapy and were negative for EGFR mutations or ALK alterations by positive or negative PD-L1 expression. In the PD-L1-positive subgroup, 1189 patients were randomized 1:1:1 to receive nivolumab/ipilimumab, nivolumab alone, or up to 4 cycles of chemotherapy. In the PD-L1-negative subgroup, 550 patients were randomized 1:1:1 to receive nivolumab/ipilimumab, chemotherapy, or nivolumab plus chemotherapy.

Chemotherapy consisted of pemetrexed plus cisplatin or carboplatin every 3 weeks for patients with nonsquamous disease or gemcitabine plus cisplatin or carboplatin every 3 weeks for patients with squamous disease.

The primary end points were OS for the PD-L1–positive population and progression-free survival (PFS) in patients with a high tumor mutational burden. The OS was previously reported at a minimum follow-up of 29.3 months with a median of 17.1 months for nivolumab/ipilimumab vs 14.9 months with chemotherapy, with 2-year OS rates of 40.0% and 32.8%, respectively.2 With the 5-year analysis, OS benefit continued to be observed with a hazard ratio of 0.77 favoring nivolumab/ipilimumab (95% CI, 0.66-0.91).1

With all patients having stopped receiving immunotherapy for at least 3 years, the efficacy versus chemotherapy has persisted in patients regardless of positive or negative PD-L1 expression.Combined 5-year OS, PFS, and DOR rates were 22%, 11%, and 27%, respectively, for those who received nivolumab/ipilimumab v 12%, 2%, and 3% for chemotherapy.

Among patients who survived for 5 years, median PFS was 59.1 months for PD-L1–positive patients and 60.7 for PD-L1–negative patients who received immunotherapy, versus 9.5 months and 24.9 months respectively for those who received chemotherapy. The median duration of response was not reached (95% CI, 52.6-NA) for PD-L1–positive patients and 59.4 months (195% CI, 8.0-NA) for PD-L1–negative patients, compared with 12.4 months (95% CI, 5.6-24.4) and 15.2 (95% CI, 2.7-NA) for those who received chemotherapy.

“In patients that survived 5 years, improved outcomes were universally observed with nivolumab and ipilimumab versus chemotherapy irrespective of PD-L1 expression,” said Brahmer in her presentation. “The majority of patients treated with nivolumab and ipilimumab did not receive subsequent therapy, with approximately two-thirds of patients remaining treatment free 3 years after discontinuing treatment.”

In contrast, among those who received chemotherapy and survived for 5 years, only 22% of PD-L1–positive patients and 17% of PD-L1–negative patients received no subsequent systemic therapy.

No new safety signals were seen in this analysis. Quality of life (QOL) was measured by an EQ-5D assessment, which showed that 5-year survivors who received nivolumab/ipilimumab reported a QOL similar to the general United States population of 79.3, significantly above the lung cancer norm of 68.0.

“These long-term results from CheckMate 227 further support nivolumab and ipilimumab as an effective first-line treatment for patients with metastatic NSCLC regardless of tumor PD-L1 expression level,” Brahmer concluded.

References

  1. Brahmer JR, Lee JS, Ciuleanu TE, et al. Five-year survival outcomes with nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for metastatic non–small cell lung cancer (NSCLC): results from CheckMate 227. J Clin Oncol. 2022;40(suppl 17):LBA9025. doi:10.1200/JCO.2022.40.17_suppl.LBA9025
  2. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381(21):2020-2031. doi:10.1056/NEJMoa1910231

Related Videos
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, on progression patterns and subsequent therapies after lorlatinib in ALK-positive NSCLC.
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, discuss preclinical CNS data for the ROS1 inhibitor zidesamtinib.
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, discuss data for zidesamtinib in ROS1-positive non–small cell lung cancer.
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, discuss data for NVL-655 in ALK-positive NSCLC and other ALK-positive solid tumors.
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, discuss testing for ALK-positive and ROS1-positive non–small cell lung cancer.
Nicolas Girard, MD
Sally Lau, MD
Andrea Wolf, MD, MPH
Jacob Sands, MD
Marina Chiara Garassino, MD