Two-Drug Combo Bests Chemotherapy in Front-Line Lung Cancer Treatment

Front-line Imfinzi (durvalumab) plus tremelimumab elicited better overall survival outcomes than standard-of-care chemotherapy for patients with metastatic non-small cell lung cancer, according to findings from a group of patients enrolled on the phase 3 NEPTUNE clinical trial that were presented at the 2022 World Conference on Lung Cancer.

Outcomes tended to vary based on expression levels of PD-L1, a protein that helps hide cancer cells from the immune system.

In particular, overall survival (time from treatment until death of any cause) was more favorable in the 55 patients with low PD-L1 status, defined as PD-L1 expression less than 1%, as well as the 160 patients in the intent-to-treat population — which is all of the patients who were involved in the study — who were treated with the frontline combination.

Overall Survival Favors Imfinzi Plus Tremelimumab

The 26 patients with PD-L1 expression less than 1% treated with the combination demonstrated a median overall survival of 15 months, compared to 11.7 months in the 29 patients treated with chemotherapy, reducing the risk for death by 40%.

This favorable overall survival trend for Imfinzi plus tremelimumab over chemotherapy was consistent across multiple time points. At 12 months, 68% of patients on the combination were alive, compared to 46.4% in the chemotherapy group. At 18 months, 44% and 39.3% of patients were alive in the combination and chemotherapy groups, respectively, and at 24 months, survival rates were 36% and 17.9%, in each group, respectively.

In the entire study population, 78 patients received the two-drug combination. Their average overall survival was 20 months — an improvement over the 82 patients who received chemotherapy and had an overall survival average of 14.1 months. Similarly, 12-, 18- and 24-month overall survival rates were superior with Imfinzi plus tremelimumab over chemotherapy at 72.8% versus 53.1%, respectively, 54.6% versus 41.8%, and 44.2% versus 30.4%.

In secondary analyses, patients with PD-L1 at or above 25% treated with Imfinzi plus tremelimumab (six patients) showed a median overall survival of 36.6 months, compared with 15.8 months in those treated with chemotherapy (four patients), reducing the risk for death by 44%. The overall survival rates also favored the combination arm in the 12-, 18- and 24-month marks at 80.6% versus 56.3% respectively; 64.5% versus 46.3%; and 54.8% versus 36.4%, in the combination group versus the chemotherapy group, respectively.

Similarly, patients with PD-L1 at or above 50% treated with the combination regimen (25 patients) demonstrated a median overall survival of 36.6 months, compared to 15.8 months with chemotherapy (28 patients), reducing the risk for death by 53%. Twelve-, 18- and 24-month overall survival rates were 84% versus 57.1%; 68% versus 45.7%; and 60% versus 34.3%, in the combination group and chemotherapy group, respectively.

Drug Combo Does Not Prolong Time to Progression

Although overall survival continually favored Imfinzi plus tremelimumab, progression-free survival, which is the time from treatment until the disease progresses or worsens, was similar between the two treatments in the primary analysis, overall study population and all PD-L1 subgroups.

In the low PD-L1 status group, median progression-free survival in the Imfinzi plus tremelimumab group was 5.1 months compared with six months. Moreover, the progression-free survival rate at 12 months was just slightly higher in the combination group at 15.6% compared with 11.3% for patients on chemotherapy.

The whole study population exhibited similar results, with a median progression-free survival of 4.2 months compared to six months in the combination and chemotherapy groups, respectively. The 12-month progression-free survival rate was higher, but not significantly, in the Imfinzi plus tremelimumab group (23.9%) compared with chemotherapy (16%).

Similarly, those with PD-L1 at or above 25% and PD-L1 at or above 50% treated with the combination regimen demonstrated a median progression-free survival of 6.8 months and 6.8 months, respectively, compared with 5.7 months and 5.7 months with chemotherapy.

Objective Response and Duration of Response

According to the researchers, response to Imfinzi plus tremelimumab depended on their PD-L1 expression. Patients on the combination therapy showed an objective response rate, which measures how much a tumor shrinks as a result of treatment, of 23.1% compared with 41.4% in patients on chemotherapy.

In the overall population, objective response rate was 35.9% in the Imfinzi plus tremelimumab group, compared to 39% in the chemotherapy arm.

Duration of response was also higher with the combination in the low PD-L1 group at 10.5 months compared with 6.1 months with chemotherapy. Median duration of response in the entire population was also higher for patients on Imfinzi plus tremelimumab at 12.9 months, compared to 6.1 months for those on chemotherapy.

More patients experienced ongoing responses at 18 months with Imfinzi plus tremelimumab in both the intent-to-treat population (46.4% versus 7.6%) and low PD-L1 expression group (33.3% versus 13.6%). According to the researchers, these results were similar in the PD-L1 50% or higher subgroup; however, these data were not shown in the poster presentation.

Lastly, Imfinzi plus tremelimumab was well tolerated with no new safety signals. In the overall population, the rate of grade 3 or 4 treatment-related side effects was lower in the Imfinzi plus tremelimumab group, compared to the chemotherapy group, at 31.2% and 52.6%, respectively.

Imfinzi Plus Tremelimumab Has a Better Side Effect Profile

The most common grade 3 or 4 side effects (serious or severe) with Imfinzi plus tremelimumab in the overall population were increased amylase, which could cause pancreas issues (9.1%), increased lipase, which could also indicate liver disease (9.1%), increased GGT, a sign of liver damage (3.9%) and diluted levels of sodium in the body (3.9%).

Six patients treated with the combination therapy had to discontinue treatment due to side effects, compared with 10 patients who received chemotherapy, including three patients who discontinued treatment due to a side effect in the combination arm. Twenty patients treated with the combination regimen experienced any immune-mediated side effect.

Median age was 62 years. Median duration of treatment at the time of data cut off was 24.9 weeks in the combination group compared with 18.9 weeks in the chemotherapy group. The majority of patients were former smokers or current smokers. Brain and liver metastases were present in 23 and 24 patients, respectively, in the overall population, and nine 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 Imfinzi plus tremelimumab may provide a better chance of living longer than treatment with chemotherapy,” the researchers concluded.

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