Prolonged Survival Observed With Nivolumab Plus Ipilimumab in Metastatic NSCLC


The 5-year analysis of the phase 3 CheckMate 227 trial showed consistent, long-term survival with nivolumab plus ipilimumab for metastatic non–small cell lung cancer.

A consistent benefit of nivolumab (Opdivo) plus ipilimumab (Yervoy) was noted at a 5-year analysis of the phase 3 CheckMate 217 trial (NCT02477826) in patients with metastatic non–small cell lung cancer, according to data presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1

The 5-year rate of overall survival (OS) was 24% in patients who received nivolumab/ipilimumab who had PD-L1 expression of at least 1%, and 19% in those with PD-L1 expression less than 1%, versus 14% and 7%, respectively, in patients who received chemotherapy. The immunotherapy combination also had a significantly higher duration of response (DOR) of 24.5 months for those with positive PD-L1 expression and 19.4 months for those with negative PD-L1 expression versus 6.7 months and 4.8 months with chemotherapy, 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 versus 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 versus 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 (52.6-NA) for PD-L1–positive patients and 59.4 months (18.0-NA) for PD-L1–negative patients, compared with 12.4 (5.6-24.4) and 15.2 (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 mNSCLC regardless of tumor PD-L1 expression level,” Brahmer concluded.


  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

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