Durvalumab in combination with tremelimumab and chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival in previously untreated patients with stage IV non–small cell lung cancer, according to findings from the final PFS analysis of the phase III POSEIDON trial.
Jose Baselga, MD, PhD
Durvalumab (Imfinzi) in combination with tremelimumab and chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in previously untreated patients with stage IV nonsmall cell lung cancer (NSCLC), according to findings from the final PFS analysis of the phase III POSEIDON trial. This met one of the dual primary end points for the ongoing trial.
“The POSEIDON trial provides evidence of the efficacy of Imfinzi in patients with stage IV nonsmall cell lung cancer. Clinical benefit was observed in a trial population that included a high proportion of patients with squamous disease and multiple choices of chemotherapy regimens. Additionally, the potential to add tremelimumab to Imfinzi and chemotherapy may present an important treatment approach in this challenging setting, especially taking into consideration the favorable safety profile,” José Baselga, MD, PhD, executive vice president of oncology research and development, AstraZeneca, said in a statement.
The randomized, open-label, multicenter, global trial is exploring the use of durvalumab and tremelimumab with standard-of-care chemotherapy in comparison with durvalumab and chemotherapy or chemotherapy alone in patients with metastatic NSCLC who do not have activatingEGFRmutations orALKfusions (NCT03164616). The trial is being conducted in 153 centers across 18 countries.
Eligible patients were those who were previously untreated with available tumor PD-L1 status and a WHO/ECOG performance status of 0 or 1. Both squamous and nonsquamous patients were included in the trial.
Patients were randomized 1:1:1 to receive either the triplet regimen, durvalumab and chemotherapy, or chemotherapy alone. Chemotherapy across the treatment arms consisted of a choice of 5 platinum-based chemotherapy regimens: nab-paclitaxel (Abraxane) and carboplatin, gemcitabine and cisplatin, gemcitabine and carboplatin, pemetrexed and carboplatin, or pemetrexed and cisplatin.
In the 2 durvalumab-based arms, the PD-L1 inhibitor is administered at a fixed dose of 1500 mg every 3 weeks when given with chemotherapy and then every 4 weeks until disease progression. Tremelimumab is administered at 75 mg every 3 weeks for 4 cycles with chemotherapy. In the triplet regimen arm, an extra dose of both durvalumab and tremelimumab is given as maintenance therapy. In the chemotherapy alone arms, chemotherapy could be given for up to 6 cycles and pemetrexed maintenance was allowed in nonsquamous patients if it was given during induction.
Dual primary end points include PFS by blinded independent central review according to RECIST 1.1 criteria and overall survival (OS). The trial will continue for the assessment of the second primary end point, with data expected in 2020.
According to data from the final PFS analysis, the PD-L1/CTLA-4/chemotherapy combination showed a broadly similar safety profile to that of durvalumab with chemotherapy, which was consistent with previous reports on the safety profile for durvalumab. The rate of discontinuation from treatment was not significantly increased with the triplet regimen.
Further findings from the POSEIDON trial are expected to be presented at an upcoming medical meeting and will be shared with regulatory authorities.
Durvalumab continues to be investigated in the phase III PEARL trial in comparison with platinum-based chemotherapy for the treatment of previously untreated patients with advanced NSCLC who do not haveEGFRmutations orALKalterations but do have high PD-L1 expression (NCT03003962).
IMFINZI® (durvalumab) and IMFINZI Plus Tremelimumab Delayed Disease Progression in Phase III POSEIDON Trial for 1st-Line Treatment of Stage IV Non-Small Cell Lung Cancer [press release]. Wilmington, DE: AstraZeneca; October 28, 2019. https://bwnews.pr/2BRfkIG. Accessed October 28, 2019.