Durvalumab/Tremelimumab Combo Provides OS Benefit in First-Line Metastatic NSCLC

The combination use of first-line durvalumab (Imfinzi) plus tremelimumab for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) improved overall survival (OS) compared with standard-of-care chemotherapy, according to an exploratory analysis of the Chinese cohort in the phase 3 NEPTUNE study (NCT02542293) presented at the IASLC 2022 World Conference on Lung Cancer.

In particular, in the open-label, international study, OS was more favorable in the 55 patients with low PD-L1 status, defined as PD-L1 <1%, and the 160 patients in the intent-to-treat (ITT) population who were treated with the frontline combination.

The 26 patients with PD-L1 <1% treated with the combination regimen demonstrated a median OS of 15.0 months (95% CI, 10.5-27.4) vs 11.7 months (95% CI, 8.6-20.5) in the 29 patients treated with chemotherapy, reducing the risk for death by 40% (HR, 0.60; 95% CI, 0.32-1.11). This favorable OS trend for durvalumab plus tremelimumab over chemotherapy was consistent at 12 (68% vs 46.4%, respectively), 18 (44% vs 39.3%), and 24 months (36% vs 17.9%).

In the ITT population, OS was also prolonged in the combination arm (n = 78) compared with the chemotherapy arm (n = 82) at a median OS of 20 months (95% CI, 15-28.7) vs 14.1 months (95% CI, 9.5-19.4), respectively (HR, 0.70; 95% CI, 0.48-1.02). Similarly, 12-, 18-, and 24-month OS rates were superior with durvalumab plus tremelimumab over chemotherapy at 72.8% vs 53.1%, respectively, 54.6% vs 41.8%, and 44.2% vs 30.4%.

In secondary analyses, patients with PD-L1 ≥25% treated with durvalumab plus tremelimumab (n = 6) showed a median OS of 36.6 months (95% CI, 15.5 to not evaluable [NE]) compared with 15.8 months (95% CI, 9-26.9) in those treated with chemotherapy (n = 4), reducing the risk for death by 44% ((HR 0.56; 95% CI, 0.29-1.07). The OS rates also favored the combination arm in the 12-, 18-, and 24-month marks at 80.6% vs 56.3%, respectively, 64.5% vs 46.3%, and 54.8% vs 36.4%.

Similarly, patients with PD-L1 ≥50% treated with the combination regimen (n = 25) demonstrated a median OS of 36.6 months (95% CI, 16.9-NE) vs 15.8 months (95% CI, 9-26.9) with chemotherapy (n = 28), reducing the risk for death by 53% (HR 0.47; 95% CI, 0.22-0.96). Twelve-, 18-, and 24-month OS rates were 84% vs 57.1%, respectively, 68% vs 45.7%, and 60% vs 34.3%,.

Although OS continually favored durvalumab plus tremelimumab, progression-free survival (PFS) was similar between the 2 treatments in the primary analysis, ITT population, and all PD-L1 subgroups. In the low PD-L1 status group, median PFS in the durvalumab plus tremelimumab arm was 5.1 months (95% CI, 2.8-7.2) compared with 6.0 months (95% CI, 4-7.5 [HR, 1.13; 95% CI, 0.59-2.14]). Moreover, the PFS rate at 12 months was just slightly higher in the combination arm at 15.6% (95% CI, 4%-34%) compared with 11.3% (95% CI, 2.3%-28.5%) for patients on chemotherapy.

The ITT population exhibited similar results, with a median PFS of 4.2 months (95% CI, 2.8-7.2 months) vs 6.0 months (95% CI, 5.5-7.5 months) in the combination and chemotherapy arms, respectively (HR, 0.95; 95% CI, 0.66-1.36). The 12-month PFS rate was higher, but not significantly, in the durvalumab plus tremelimumab group (23.9%; 95% CI, 14.8%-34.2%) compared with chemotherapy (16%; 95% CI, 8.5%-27%).

Similarly, those with PD-L1 ≥25% and PD-L1 ≥50% treated with the combination regimen demonstrated a median PFS of 6.8 months (95% CI, 4.1-8.4) and 6.8 months (95% CI, 4.2-20.2), respectively, compared with 5.7 months (95% CI, 4.2-8.5) and 5.7 months (95% CI, 4.2-8.5) with chemotherapy.

According to the researchers, response to durvalumab plus tremelimumab depended on their PD-L1 expression. Patients on the combination therapy showed an objective response rate (ORR) of 23.1% compared with 41.4% in patients on chemotherapy (odds ratio [OR], 0.42; 95% CI, 0.12-1.34). In the ITT population, ORR was 35.9% in the durvalumab plus tremelimumab arm vs 39% in the chemotherapy arm (OR, 0.87; 95% CI, 0.45-1.66).

Duration of response (DOR) was also higher with the combination in the low PD-L1 group at 10.5 months compared with 6.1 months with chemotherapy (HR, 0.79; 95% CI, 0.18-2.86). Median DOR in the ITT population was also higher for patients on durvalumab plus tremelimumab at 12.9 months vs 6.1 months for those on chemotherapy (HR, 0.39; 95% CI, 0.19-0.76). More patients experienced ongoing responses at 18 months with durvalumab plus tremelimumab in both the ITT population (46.4% vs 7.6%) and low PD-L1 expression group (33.3% vs 13.6%). According to the researchers, these results were similar in the PD-L1 ≥50% subgroup; however, these data were not shown in the poster presentation.

Lastly, durvalumab plus tremelimumab was well tolerated with no new safety signals. In the overall population, the rate of grade 3 or 4 treatment-related adverse events (TRAEs) was lower in the durvalumab plus tremelimumab arm vs chemotherapy (31.2% vs 52.6%, respectively). The most common grade 3 or 4 TRAEs with durvalumab plus tremelimumab in the overall population were increased amylase (9.1%), increased lipase (9.1%), increased GGT (3.9%), and hyponatremia (3.9%). Six patients treated with the combination therapy had to discontinue treatment due to AEs compared with 10 patients who received chemotherapy, including 3 patients who discontinued treatment due to a TRAE in the combination arm. Twenty patients treated with the combination regimen experienced any immune-mediated AE.

Median age was 62 years. Median duration of treatment at the time of data cut off was 24.9 weeks in the combination arm compared with 18.9 weeks in the chemotherapy arm. The majority of patients were former smokers (ITT population, n = 89; low PD-L1 group, n = 34) or current smokers (ITT population, n = 26; low PD-L1 group, n = 7). Brain and liver metastases were present in 23 and 24 patients, respectively, in the ITT population, and 9 and 10 patients, respectively, in the low PD-L1 group.

“Our findings suggest that, among Chinese patients with metastatic NSCLC, those with low PD-L1 levels and also those in the whole cohort, treatment with durvalumab plus tremelimuab may provide a better chance of living longer than treatment with chemotherapy,” the researchers concluded.

Reference

1. Cheng Y, Zhou Q, Han B, et al. NEPTUNE China Cohort: First-Line Durvalumab + Tremelimumab versus Chemotherapy in Chinese Patients with Metastatic NSCLC. Presented at: IASLC 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Poster EP08.01-42.