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CCTG BR.31 Data Show Adjuvant Durvalumab Does Not Alter Relapse Frequency or Patterns in Resected NSCLC

Adjuvant durvalumab was not associated with a reduction in the frequency of relapse in NSCLC.

Image Credit:©catalin – stock.adobe.com

Image Credit:©catalin – stock.adobe.com

Adjuvant durvalumab (Imfinzi) was not associated with a reduction in the frequency of relapse or alterations in the patterns of relapse compared with placebo in patients with resected stage IB to IIIA non–small cell lung cancer (NSCLC) who did not harbor EGFR or ALK alterations, irrespective of PD-L1 status, according to data from an analysis of the phase 3 CCTG BR.31 trial (NCT02273375).1

Findings presented at the 2025 European Lung Cancer Congress showed that in all patients without EGFR or ALK alterations, those treated with durvalumab (n = 815) experienced a relapse rate of 36.4% compared with 37.1% for those given placebo (n = 404). Among patients with a PD-L1 expression of at least 25%, the relapse rates were 33.2% for durvalumab (n = 316) vs 32.3% for placebo (n = 161). In patients with a PD-L1 expression of at least 1%, the relapse rates were 35.8% for durvalumab (n = 469) compared with 33.7% for placebo (n = 240).

Additionally, secondary cancers were reported in 5.3% of the overall population treated with durvalumab vs 8.7% of patients given placebo. In the population of patients with a PD-L1 expression of at least 25%, these rates were 6% and 8.7%, respectively. In the subgroup of patients with a PD-L1 expression of at least 1%, the secondary cancer rates were 5.8% for durvalumab vs 8.8% for placebo.

“Adjuvant durvalumab did not reduce the frequency or alter [the] pattern of relapses regardless of PD-L1 status in patients with EGFR-negative and ALK-negative NSCLC who had undergone complete resection,” lead study author Virginie Westeel, MD, PhD, of CHRU Besancon-Hopital Jean Minjoz in France, said in a presentation of the data.

Previously reported data from CCTG BR.31 presented at the 2024 ESMO Congress showed that at a median follow-up of 60.0 months, patients with resected NSCLC without EGFR or ALK alterations and a PD-L1 expression of at least 25% treated in the durvalumab arm (n = 316) achieved a median disease-free survival (DFS) of 69.9 months (95% CI, 57.6-not reached [NR]) compared with 60.2 months (95% CI, 47.7-NR) for those given placebo (n = 161; HR, 0.935; 95% CI, 0.706-1.247; P = .642).2

In the population of patients with a PD-L1 expression of at least 1%, the median DFS was 59.9 months (95% CI, 48.4-77.9) for durvalumab (n = 469) vs 60.3 months (95% CI, 43.8-80.9) for placebo (n = 240; HR, 0.989; 95% CI, 0.788-1.248; P = .926). In the all-comers population, the median DFS was 60.0 months (95% CI, 49.6-74.9) for durvalumab (n = 815) vs 53.9 months (95% CI, 36.7-67.3) for placebo (n = 404; HR, 0.893; 95% CI, 0.752-1.065; P = .207).

CCTG BR.31 Background

The phase 3 study enrolled patients with completely resected stage IB (≥4 cm) to IIIA NSCLC per the seventh edition of American Joint Commission on Cancer staging criteria.1 Notably, those harboring EGFR or ALK alterations were allowed to enroll; however, they were not included in this analysis. Patients needed to have an ECOG performance status of 0 or 1.

Prior to randomization, all patients were allowed the receive platinum-doublet chemotherapy as adjuvant treatment. At least 3 weeks following surgery, patients were randomly assigned in a 2:1 fashion to receive durvalumab at 20 mg/kg or placebo once every 4 weeks for up to 12 months.

Stratification factors included stage (IB vs II vs IIIA), PD-L1 status (0% vs 1%-24% vs 25%-49% vs ≥50%), adjuvant chemotherapy (≥300 mg/m2 of cisplatin or equivalent vs <300 mg/m2 of cisplatin or equivalent vs no chemotherapy), accruing center, and nodal dissection status (yes vs no).

Investigator-assessed DFS in the population of patients without EGFR/ALK alterations and with a PD-L1 expression of at least 25% served as the trial’s primary end point. DFS in other populations, overall survival, safety, and quality of life were secondary end points.

Additional Relapse Data

Among evaluable all-comer patients in the durvalumab who experienced disease relapse (n = 297), 57% of patients had locoregional-only, relapse 57% had distant-only relapse, and 19% had both locoregional and distant relapse. In the placebo arm (n = 150), these rates were 18%, 62%, and 20%, respectively. In this group of patients, 16% of patients in the durvalumab arm vs 19% in the placebo arm had brain-only distant relapses.

In the population of patients with a PD-L1 expression of at least 25%, patterns of relapse were also similar between the durvalumab arm (n = 105) and placebo arm (n = 52) in terms of locoregional-only relapse (durvalumab, 24%; placebo, 29%), distant-only relapse (61%; 52%), locoregional and distant relapse (15%; 19%), and brain-only relapse (20%; 17%). Sites of distant relapses in this population included lung (durvalumab, n = 34; placebo, n = 16), brain (n = 25; n = 12), distant lymph nodes (n = 12; n = 10), pleural (n = 15; n = 9), bone (n = 7; n = 4), adrenal (n = 6; n = 2), and liver (n = 4; n = 3).

Furthermore, a descriptive analysis, which did not account for censored patients, showed that in the all-comers in the durvalumab arm experienced locoregional-only relapse at a median of 14 months after randomization, distant-only relapse at a median of 12 months, locoregional plus distant relapse at a median of 14 months, and brain-only relapse at a median of 10 months. In the placebo arm, these times respective times were 8 months, 8 months, 11 months, and 11 months.

In the population of patients with a PD-L1 expression of at least 25% treated with durvalumab, the median time to locoregional-only relapse was 13 months, the median time to distant-only relapse was 14 months, the median time to locoregional plus distant relapse was 13 months, and the median time to brain-only relapse was 11 months. These values were 8 months, 8 months, 14 months, and 16 months, respectively, in the placebo group.

Patients with a PD-L1 expression of at least 1% treated with durvalumab experienced median time to locoregional-only relapse of 14 months, a median time to distant-only relapse of 14 months, a median time to locoregional plus distant relapse of 14 months, and a median time to brain-only relapse of 15 months. In the placebo group, these respective values were 9 months, 8 months, 13 months, and 16 months.

Among patients in the overall population who experienced distant relapse with or without locoregional relapse, 88% of those in the durvalumab arm and 94% of patients in the placebo arm received any subsequent therapy. In the durvalumab arm, subsequent therapies included chemotherapy (53%), immunotherapy (21%), and targeted therapy (24%). These respective rates were 50%, 31%, and 31% in the placebo group.

In the population of patients with a PD-L1 expression of at least 25%, 91% of patients in the durvalumab arm who experienced distant relapse received subsequent therapy vs 97% of patients in the placebo arm. Subsequent therapies in the durvalumab group included chemotherapy (50%), immunotherapy (26%), and targeted therapy (19%). These rates were 54%, 46%, and 24%, respectively, in the placebo group.

For patients with a PD-L1 expression of at least 1% who experienced distant relapse, 90% in the durvalumab arm and 94% in the placebo arm were administered subsequent therapy, which included chemotherapy (durvalumab, 52%; placebo, 52%), immunotherapy (24%; 40%), and targeted therapy (21%; 22%).

In the all-comers population, subsequent therapies in the durvalumab arm for patients who had locoregional-only relapses (n = 72) included surgery (9.7%) and radiotherapy (65.3%); these respective rates were 7.4% and 74.1% in the placebo arm (n = 27). For patients with brain-only relapses in the durvalumab arm (n = 48), additional therapy included surgery (41.7%) and radiotherapy (85.4%); these rates were 41.4% and 75.9%, respectively, in the placebo group.

In the subgroup of patients with a PD-L1 expression of at least 25%, patients in the durvalumab arm who had locregional-only relapses (n = 25) received subsequent surgery (12%) or radiotherapy (76%); these respective rates were 13.3% and 73.3% for the placebo group (n = 15). In those with brain-only relapses, 47.6% and 90.5% of patients in the durvalumab group (n = 21) received subsequent surgery and radiotherapy, respectively. These rates were both 77.8% in the placebo group (n = 9).

For those with a PD-L1 expression of at least 1%, subsequent treatments for locoregional-only relapse included surgery (8.9%) and radiotherapy (66.7%) for the durvalumab arm (n = 45); these respective rates were 11.1% and 72.2% in the placebo group (n = 18). For those with brain-only relapses, subsequent therapies in the durvalumab arm (n = 30) included surgery (43.3%) and radiotherapy (83.3%); in the placebo group (n = 12), these rates were both 66.7%.

Disclosures: Westeel reported personal financial interests with Amgen, MSD, Roche, Bristol Myers Squibb, Pfizer, and Sanofi; institutional financial interests with Amgen, Bristol Myers Squib, Daiichi, Ose Immunotherapeutics, Roche, Seagen, Merck, and MSD; and receiving travel support from Amgen, AstraZeneca, Bristol Myers Squib, Janssen, and MSD.

References

  1. Westeel V, Goss G, Darling GE, et al. Sites of relapse and subsequent therapy in the BR.31 phase III study of durvalumab vs placebo in resected stage IB-IIIA NSCLC. J Thorac Oncol. 2025;20(suppl 1):S98-S99. doi:10.1016/S1556-0864(25)00330-2
  2. Goss G, Darling GE, Westeel V, et al. CCTG BR.31: A global, double-blind placebo-controlled, randomized phase III study of adjuvant durvalumab in completely resected non-small cell lung cancer (NSCLC). Ann Oncol. 2024;35(suppl 2):S1238. doi:10.1016/j.annonc.2024.08.2289 External Link

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