Durvalumab Associated With Lower Real-World PFS in EGFR-Mutated NSCLC Vs EGFR Wild-Type NSCLC

Treatment with durvalumab (Imfinzi) was associated with lower real-world progression-free survival (rwPFS) in patients with unresectable, stage III EGFR-mutated non–small cell lung cancer (NSCLC) vs patients with EGFRwild-type disease, according to data from the observational PACIFIC-R trial (NCT03798535) presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.¹

Overall survival (OS) rates were similar between patients with EGFR-mutated NSCLC and patients with EGFR-wildtype NSCLC. However, the median rwPFS was 10.6 months (95% CI, 8.7-27.3) in the EGFR-mutated population vs 26.4 months (95% CI, 20.5-35.7) in the EGFR wild-type population.

“Outcomes for patients with EGFR-mutated NSCLC were consistent with PFS and OS findings for the same subpopulation in the founder [phase 3] PACIFIC trial [NCT02125461]. These data should be interpreted carefully, of course, due to the small number with identified EGFR-mutated [disease] in the PACIFIC-R study, as well as its retrospective nature. The ongoing phase 3 LAURA trial [NCT03521154] is evaluating the efficacy and safety of maintenance osimertinib [Tagrisso] in patients with unresectable, stage III EGFR-mutated NSCLC who have not demonstrated progression after chemoradiation," Solange Peters, MD, PhD, professor and chair of medical oncology and the thoracic malignancies programme in the Department of Oncology at the University Hospital of Lausanne in Switzerland, said during the presentation.

Consistent with the results from the phase 3 PACIFIC trial,2 which established durvalumab as the global standard of care as up to 12 months treatment for patients with stage III NSCLC, the PACIFIC-R trial shows variation in efficacy with this tumor type. The effectiveness regarding consolidation immunotherapy in patients with EGFR-mutated NSCLC remain uncertain, which, in turn, led to the PACIFIC-R trial. However, the 5-year PFS rates reported a stratified HR of 0.55 (95% CI, 0.45-0.68) and the 5-year PFS rate is 33.1% for patients with EGFR wild-type NSCLC vs 19.0% for those with EGFR-mutated disease. The 5-year OS reported a stratified HR of 0.72 (95% CI: 0.59–0.89), and the 5-year OS rate is 42.9% vs 33.4%, respectively.¹

PACIFIC-R trial a retrospective observational study reviewing medical records that comprised of 1154 patients from 10 countries. The end date for the review was November 30, 2021. Among the patients involved in the study, 466 had a known EGFR status revealed through local testing (422 EGFR wild-type and 44 EGFR-mutated). There was a higher percentage of patients with EGFR-mutated NSCLC that had never smoked (20.5% vs 10.9%) and were 70 year of age or older (40.9% vs 27.3%) compared to patients with EGFR wild-type NSCLC.

The primary end points for the study were investigator assessed rwPFS and OS using Kaplan-Meier assessments. The rwPFS and OS regarding EGFR status was an exploratory goal.

Patients eligible for the study, had unresectable stage III NSCLC, were 18 years or older, did not show progression after sequential or platinum-based chemoradiotherapy, and were enrolled in a preliminary program initiated by AstraZeneca. In the program patients received 10 mg/kg of durvalumab intravenously every 2 weeks between September 2017 and December 2018.

There was a difference of 76.3% and 76.9% patients with available PD-L1 test results with an expression level of 1% or greater in the groups with EGFR-mutated group and EGFR-wild group, respectively. For the patient group with EGFR-mutated NSCLC the EGFR inhibitors were administered after durvalumab as the first subsequent treatment in 15/20 patients who had distant metastases.¹

Adverse effects (AEs) experienced by patients were primarily pneumonitis 9 (20.5%), endocrinopathies 7 (15.9%), rash/dermatitis 4 (9.1%), and gastrointestinal disorders 2 (4.5%). A portion of patients with EGFR-mutated NSCLC experienced AE of special interest (56.8%), and these were limited to events that occurred during the durvalumab treatment and up to 90 days after the last infusion or initiation of subsequent therapy.¹ Only 11.4% AEs led to discontinuation of durvalumab.

Regarding futher study, the ongoing phase 3 LAURA trial (NCT03521154)3 is currently working to evaluate the efficacy and safety of maintenance Osimertinib (Tagrisso) for patients who have unresectable stage III, EGFR-mutated NSCLC and who experienced no progression after chemotherapy.¹ Patients eligible for the trial must be 18 years or older and with locally advanced, unrespectable stage III NSCLC with local/central confirmation of an EGFR exon 19 deletion/L858R mutation.³

References

1. Peters, S., Christoph, D.C., Field, J.K., et al. OA17.03 Real-world outcomes with durvalumab after chemoradiotherapy in unresectable stage III EGFR-mutated NSCLC (PACIFIC-R). Presented at: International Association for the study of lung cancer 2023 World Conference on Lung Cancer; September 9-12, 2023; Singapore. Abstract OA17.03.
2. Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350. doi:10.1056/NEJMoa1809697
3. Lu S, Casarini I, Kato T, et al. Osimertinib maintenance after definitive chemoradiation in patients with unresectable EGFR mutation positive stage III non-small-cell lung cancer: LAURA Trial in Progress. Clin Lung Cancer. 2021;22(4):371-375. doi:10.1016/j.cllc.2020.11.004