Nivolumab increases the 1-year survival rate in patients with non-squamous non-small cell lung cancer
The treatment options for patients with non-squamous non-small cell lung cancer (NSCLC) with disease progression after platinum-based chemotherapy are limited. Currently, the second-line therapy for these patients consists of a second round of chemotherapy with either docetaxel, or pemetrexed. Previously reported data of the Checkmate-057 trial suggested that nivolumab is a better second-line treatment option for these patients and updated results of this study, presented during the 2015 European Cancer Congress, confirm this.
The updated data demonstrate that after 12 months of therapy, 51% of patients were still alive in the nivolumab treated cohort compared to 39% with docetaxel. After 6 more months of follow up (18 months in total), this difference in overall survival (OS) rate was maintained at 39% survivors with nivolumab compared to 23% with docetaxel.
In the international, randomized, phase III Checkmate-057 study, a total of 582 patients with non-squamous NSCLC with disease progression after platinum-based chemotherapy were randomly assigned to receive nivolumab (3 mg/kg IV, every 2 weeks) (N=292), or docetaxel (75 mg/m2 IV, every 3 weeks) (N=290). Patients in the study were treated until progression, or until the treatment-related toxicity was deemed unacceptable.
The updated analysis demonstrated that patients in the nivolumab arm had a significantly higher chance of being alive after 12 and 18 months in comparison to patients who were assigned to the docetaxel treatment. In fact, the overall survival (OS) rate at 12 months was 51% and 39% for nivolumab and docetaxel respectively. After 18 months 39% of the nivolumab treated patients were still alive compared to 23% with docetaxel. The median OS for patients assigned to the nivolumab treatment was 12.2 months, versus 9.4 months with docetaxel (HR[95%CI]: 0.72[0.60-0.88]; p= 0.0009). The reported objective response rate (ORR) was 19% with nivolumab versus 12% with docetaxel (OR[95%CI]: 1.7[1.1-2.6]; p= 0.0246). Finally, also the median duration of response was significantly longer with nivolumab at 17.2 months compared to 5.6 months with docetaxel.
The survival advantage of nivolumab over docetaxel was observed irrespective of the PD-L1 expression status. However, the investigators did observe that the benefit of nivolumab over docetaxel increased with a higher expression of PD-L1. In fact, the HR for OS for nivolumab versus docetaxel was 0.59 (95%CI: 0.43-0.82) with a PD-L1 expression in 1% or more of the tumor cells, while this HR decreased to 0.43 (95%CI: 0.30-0.63) and 0.40 (95%CI: 0.26-0.59) in samples with a PD-L1 expression in respectively 5% or more and 10% or more of the cells. In addition, the ORR was higher in case of a higher PD-L1 expression. In the cohort of patients with PD-L1 expression in 1% or more of the cells, the ORR was 31% compared with only 9% in the cases with a PD-L1 expression below 1%. On the other hand, the PD-L1 did not seem to have an influence on the duration of response with a median duration of 16 months in case of a PD-L1 expression of 1% or more and of 18.3 months in patients with a PD-L1 expression below 1%. For patients receiving docetaxel, the median duration of response was 5.6 months, irrespective of the PD-L1 expression status.
Interestingly, patients in the nivolumab arm of the study had a lower incidence of grade 3/4 treatment-related adverse events than patients treated with docetaxel: 20% vs. 54%. The incidence of grade 3/4 adverse events was not influenced by the PD-L1 expression. The incidence of grade 3/4 adverse events with nivolumab and docetaxel was 13% and 53% respectively in patients with a PD-L1 expression of 1% or more, and 8% and 58% in patients with PD-L1 expression in less than 1% of the cells. In line with what was previously reported with nivolumab in lung cancer, ever-smokers seemed to be somewhat more likely to respond to the anti-PD1 therapy than patients who never smoked (22% vs. 9%). In the docetaxel arm, no correlation was seen between smoking history and response with an ORR of 11% in de ever-smokers and 15% in the never-smokers. Looking at the EGFR mutation status in relationship to response, nivolumab treated EGFR mutated patients had an ORR of 11% compared to an ORR of 18% in patients with wild-type EGFR. For docetaxel these rates were 16% and 9% respectively.
In summary, these findings strongly support the use of nivolumab in the second-line treatment of non-squamous NSCLC.
Horn L, et al. Phase 3, randomized trial (CheckMate 057) of nivolumab (NIVO) vs docetaxel (DOC) in advanced non-squamous (non-SQ) non-small cell lung cancer (NSCLC): Subgroup analyses and patient reported outcomes (PROs). Presented at ECC 2015; Abstract #3010.