Durvalumab Combo Misses PFS End Point in Unresectable Stage III NSCLC

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The safety profile of durvalumab plus chemoradiation among patients with unresectable non–small cell lung cancer in the phase 3 PACIFIC-2 trial appears to be consistent with prior reports.

 “While the PACIFIC-2 trial results did not show what we hoped, the PACIFIC regimen remains the standard of care for patients with unresectable, stage III [NSCLC],” according to Jeffrey D. Bradley, MD.

“While the PACIFIC-2 trial results did not show what we hoped, the PACIFIC regimen remains the standard of care for patients with unresectable, stage III [NSCLC],” according to Jeffrey D. Bradley, MD.

Administering durvalumab (Imfinzi) concurrently with chemoradiotherapy (CRT) did not produce a statistically significant improvement in progression-free survival (PFS) compared with CRT by itself among patients with unresectable stage III non–small cell lung cancer (NSCLC), according to a press release on findings from the phase 3 PACIFIC-2 trial (NCT03519971).

Data indicated that the safety profile of durvalumab plus CRT was comparable with previous reports of each respective treatment. However, investigators observed that a higher proportion of patients in the experimental arm experienced infections during concurrent treatment with durvalumab plus CRT. Treatment with durvalumab following platinum-based CRT was established as a standard of care for this patient population based on results from the phase 3 PACIFIC trial (NCT02125461).

“While the PACIFIC-2 trial results did not show what we hoped, the PACIFIC regimen remains the standard of care for patients with unresectable, stage III [NSCLC],” principal investigator Jeffrey D. Bradley, MD, vice chair of Proton Therapy & Technology Development at Penn Medicine in Philadelphia, said in the press release. “As a community, we will take insights from these results to advance future research.”

Investigators of the phase 3 PACIFIC-2 trial assessed concurrent administration of durvalumab plus CRT among a population of patients who experienced disease progression or discontinued treatment during CRT. Patients were assigned to receive durvalumab or matched placebo intravenously plus CRT, with chemotherapy agents including cisplatin/etoposide, carboplatin/paclitaxel, pemetrexed/cisplatin, or pemetrexed/carboplatin. Those who had a complete or partial response or stable disease after completing CRT were eligible to continue consolidation therapy with durvalumab or placebo.

The trial’s primary end point was PFS. Secondary end points included overall survival, objective response rate, duration of response, disease control rate, PFS2, time to distant metastasis or death, health-related quality of life, and pharmacokinetics.

Patients 18 years and older with histologically or cytologically confirmed NSCLC that was locally advanced and unresectable were able to enroll on the study. Additional eligibility criteria included having a World Health Organization performance status of 0 or 1 and at least 1 measurable lesion not previously managed with radiation. Patients also needed to have a life expectancy of 12 weeks or more at the time of randomization.

Those who received prior or current cancer treatment including radiotherapy, investigational agents, durvalumab, and monoclonal antibodies were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had a history of allogenic organ transplantation, uncontrolled intercurrent illness, another primary malignancy, mixed small cell and NSCLC histology, any medical contraindication to treatment with platinum-based doublet chemotherapy, and active or previously documented autoimmune or inflammatory disorders. Additionally, having any active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus was grounds for exclusion from the trial.

“Our goal with the PACIFIC-2 trial was to address a remaining unmet need for patients in this setting by introducing immunotherapy even earlier and concurrently administering [durvalumab] with [CRT],” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, concluded. “While today’s results did not reach statistical significance, we will learn from this trial, and we remain committed to improving patient outcomes by expanding the benefit of immunotherapy to patients [with lung cancer] across treatment settings.”

Reference

Update on PACIFIC-2 phase III trial of Imfinzi concurrently administered with platinum-based chemoradiotherapy in unresectable, stage III non-small cell lung cancer. News release. AstraZeneca. November 14, 2023. Accessed November 14, 2023. https://shorturl.at/bmpFW

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