Durvalumab plus tremelimumab plus chemotherapy

POSEIDON (NCT03164616), a phase III open-label trial, studied tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, and chemotherapy alone as first-line therapy in patients with metastatic NSCLC. The primary end points were PFS and OS for durvalumab plus chemotherapy versus chemotherapy. Key alpha-controlled secondary end points were PFS and OS for tremelimumab plus durvalumab and chemotherapy versus chemotherapy. Patients were randomly assigned (1:1:1) to one of the following three arms:[97][Level of evidence B1]The following results were observed:

POSEIDON (NCT03164616), a phase III open-label trial, studied tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, and chemotherapy alone as first-line therapy in patients with metastatic NSCLC. The primary end points were PFS and OS for durvalumab plus chemotherapy versus chemotherapy. Key alpha-controlled secondary end points were PFS and OS for tremelimumab plus durvalumab and chemotherapy versus chemotherapy. Patients were randomly assigned (1:1:1) to one of the following three arms:[97][Level of evidence B1]The following results were observed:

Arm 1: Tremelimumab 75 mg plus durvalumab 1,500 mg with platinum-based chemotherapy for up to four 21-day cycles followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose at week 16.

POSEIDON (NCT03164616), a phase III open-label trial, studied tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, and chemotherapy alone as first-line therapy in patients with metastatic NSCLC. The primary end points were PFS and OS for durvalumab plus chemotherapy versus chemotherapy. Key alpha-controlled secondary end points were PFS and OS for tremelimumab plus durvalumab and chemotherapy versus chemotherapy. Patients were randomly assigned (1:1:1) to one of the following three arms:[97][Level of evidence B1]The following results were observed:

Arm 2: Durvalumab plus chemotherapy for up to four 21-day cycles followed by durvalumab once every 4 weeks until progression.

POSEIDON (NCT03164616), a phase III open-label trial, studied tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, and chemotherapy alone as first-line therapy in patients with metastatic NSCLC. The primary end points were PFS and OS for durvalumab plus chemotherapy versus chemotherapy. Key alpha-controlled secondary end points were PFS and OS for tremelimumab plus durvalumab and chemotherapy versus chemotherapy. Patients were randomly assigned (1:1:1) to one of the following three arms:[97][Level of evidence B1]The following results were observed:

Arm 3: Platinum-based chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed).

POSEIDON (NCT03164616), a phase III open-label trial, studied tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, and chemotherapy alone as first-line therapy in patients with metastatic NSCLC. The primary end points were PFS and OS for durvalumab plus chemotherapy versus chemotherapy. Key alpha-controlled secondary end points were PFS and OS for tremelimumab plus durvalumab and chemotherapy versus chemotherapy. Patients were randomly assigned (1:1:1) to one of the following three arms:[97][Level of evidence B1]The following results were observed:

Treatment with durvalumab significantly improved PFS compared with chemotherapy alone. The median PFS was 5.5 months for patients who received durvalumab plus chemotherapy and 4.8 months for patients who received chemotherapy alone (HR, 0.74; 95% CI, 0.62–0.89; P = .0009).

POSEIDON (NCT03164616), a phase III open-label trial, studied tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, and chemotherapy alone as first-line therapy in patients with metastatic NSCLC. The primary end points were PFS and OS for durvalumab plus chemotherapy versus chemotherapy. Key alpha-controlled secondary end points were PFS and OS for tremelimumab plus durvalumab and chemotherapy versus chemotherapy. Patients were randomly assigned (1:1:1) to one of the following three arms:[97][Level of evidence B1]The following results were observed:

A trend for improved OS did not reach statistical significance for patients in arms 2 and 3. The median OS was 13.3 months for patients who received durvalumab plus chemotherapy and 11.7 months for patients who received chemotherapy alone. (HR, 0.86; 95% CI, 0.72–1.02; P = .0758). The 24-month OS rate was 29.6% in the durvalumab-plus-chemotherapy arm and 22.1% in the chemotherapy-alone arm.

POSEIDON (NCT03164616), a phase III open-label trial, studied tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, and chemotherapy alone as first-line therapy in patients with metastatic NSCLC. The primary end points were PFS and OS for durvalumab plus chemotherapy versus chemotherapy. Key alpha-controlled secondary end points were PFS and OS for tremelimumab plus durvalumab and chemotherapy versus chemotherapy. Patients were randomly assigned (1:1:1) to one of the following three arms:[97][Level of evidence B1]The following results were observed:

Both PFS and OS were significantly improved when tremelimumab therapy was added to durvalumab and chemotherapy compared with chemotherapy alone. The median PFS was 6.2 months for patients who received tremelimumab plus durvalumab and chemotherapy and 4.8 months for patients who received chemotherapy alone (HR, 0.72; 95% CI, 0.60–0.86; P = .0003). The median OS was 14.0 months in the tremelimumab arm and 11.7 months in the chemotherapy-alone arm (HR, 0.77; 95% CI, 0.65–0.92; P = .0030). The 24-month OS rate was 32.9% in the tremelimumab-plus durvalumab-and-chemotherapy arm and 22.1% in the chemotherapy-alone arm. In addition, this combination demonstrated consistent OS results across levels of PD-L1 expression.

POSEIDON (NCT03164616), a phase III open-label trial, studied tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, and chemotherapy alone as first-line therapy in patients with metastatic NSCLC. The primary end points were PFS and OS for durvalumab plus chemotherapy versus chemotherapy. Key alpha-controlled secondary end points were PFS and OS for tremelimumab plus durvalumab and chemotherapy versus chemotherapy. Patients were randomly assigned (1:1:1) to one of the following three arms:[97][Level of evidence B1]The following results were observed:

Grade 3 to 4 treatment-related events occurred in 51.8% of patients who received tremelimumab plus durvalumab and chemotherapy, 14.1% of patients who received durvalumab and chemotherapy, and 9.9% of patients who received chemotherapy alone.