Clinical trialPhase 3Lung cancer

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer

J Clin Oncol · 2022713 patients

Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, et al. J Clin Oncol. 2022. 40:1301-1311

Study type: Clinical trial
Study name: PACIFIC
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial (2:1); this paper reports updated exploratory analyses about 5 years after the last randomisation
Sample size: 713 patients
Source: J Clin Oncol · 2022
Trial registration: NCT02125461

In plain words

In stage III lung cancer that cannot be operated on, after finishing chemotherapy and radiotherapy given together, one year of the immunotherapy drug durvalumab (an infusion every 2 weeks) raised the chance of being alive after 5 years from about 33% to about 43%, and almost a third of patients had no worsening of their disease after 5 years.

Key results

42.9% vs 33.4%

5-year overall survival

47.5 vs 29.1 months

Median overall survival

Stratified HR 0.72; 95% CI: 0.59 to 0.89

33.1% vs 19.0%

5-year progression-free survival

16.9 vs 5.6 months

Median progression-free survival

HR 0.55; 95% CI: 0.45 to 0.68

HR 0.68

Overall survival (primary analysis)

95% CI: 0.53 to 0.87; P=0.00251

Drugs in this study:Durvalumab (Imfinzi)

Dose and schedule cards

Consolidation durvalumab after chemoradiotherapy (PACIFIC)

Unresectable stage III NSCLC without progression after at least 2 cycles of platinum chemotherapy concurrent with radiotherapy; WHO PS 0–1; with an EGFR mutation, osimertinib (next regimen) is preferredCycle length: Every 14 or 28 daysOn the page “Lung cancer” · Unresectable stage III NSCLC: chemoradiotherapy and consolidation therapy

Drug	Dose	Route	Schedule
Durvalumab	10 mg/kg every 2 weeks or 1500 mg every 4 weeks (body weight ≥30 kg)	IV (60 min)	Start within 42 days after the end of chemoradiotherapy

Cycle length: Every 14 or 28 days
Duration: Up to 12 months, or until progression or intolerable toxicity

Source: FDA label for durvalumab; 5-year results. In PACIFIC, pneumonitis (including radiation pneumonitis) occurred in 18.3% of the durvalumab group vs 12.8% of the placebo group.

On the page “Lung cancer” · Unresectable stage III NSCLC: chemoradiotherapy and consolidation therapy

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Durvalumab

Durvalumab 10 mg/kg IV every 2 weeks for up to 12 months; starting 1 to 42 days after completion of concurrent chemoradiotherapy. Treatment stopped for confirmed progression, start of another anticancer therapy, unacceptable toxicity or withdrawal (476 patients randomised; 473 treated). The current FDA label also allows 1500 mg every 4 weeks for patients ≥30 kg as an alternative to 10 mg/kg every 2 weeks (up to 12 months).

2Placebo

IV placebo every 2 weeks for up to 12 months with the same discontinuation rules (237 patients; 236 treated).

Source of the regimen details: Full text of the JCO 2022 paper (PMC9015199) and the FDA label for Imfinzi (DailyMed, sections 2.2 and 14.1, September 2026 version)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with unresectable stage III NSCLC (AJCC 7th edition), WHO performance status zero or 1, without progression after at least 2 cycles of concurrent platinum-based chemoradiotherapy (total radiation dose usually 60 to 66 Gy in 30 to 33 fractions); regardless of PD-L1 expression; randomisation 1 to 42 days after chemoradiotherapy. Exclusion criteria: unresolved grade >2 toxicity or grade ≥2 pneumonitis from chemoradiotherapy, active or prior autoimmune disease within the past 2 years, and need for systemic immunosuppression. Stratified by age, sex and smoking history.

Endpoints

Primary endpoints: overall survival and progression-free survival (blinded independent central review, RECIST 1.1). This paper is a 5-year exploratory update.

Safety and side effects

In the primary overall survival analysis, grade 3 or 4 adverse events of any cause occurred in 30.5% of the durvalumab group and 26.1% of the placebo group (fatal adverse events 4.4% vs 6.4%); 15.4% and 9.8% discontinued treatment because of adverse events (mostly pneumonitis, radiation pneumonitis and pneumonia). 49.0% vs 34.7% completed the 12-month course. Per the FDA label: serious adverse events 29% (pneumonitis or radiation pneumonitis 7%, pneumonia 6%); durvalumab discontinued because of pneumonitis/radiation pneumonitis in 6%.

Clinical significance and place in guidelines

PACIFIC made the "PACIFIC regimen" (concurrent chemoradiotherapy followed by one year of durvalumab) the standard of care for unresectable stage III NSCLC (FDA approval in February 2018). In patients with EGFR mutations, osimertinib (LAURA trial) has replaced it. The ESMO and NCCN guidelines recommend this regimen; the EMA has restricted its use to tumours with PD-L1 ≥1%.

Limitations

The 5-year analysis is exploratory; PD-L1 status was not required at enrolment and many patients had no evaluable sample; patients with sequential chemoradiotherapy or progression during it were not enrolled; EGFR/ALK mutation status was not systematically assessed.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.