A proportion of cancer patients treated with anti-programmed cell death-1 (PD-1) and its ligand (PD-L1) achieve long-lasting responses. Some of these patients stop treatment without disease progression (DP). Limited data exist on re-initiation of the same PD-1/PD-L1 inhibitor upon progression.
In NCT01693562, a phase I/II study evaluating durvalumab in advanced solid tumors, patients were treated until DP or up to 1 year. Per protocol, patients who benefited from durvalumab and stopped treatment after 1 year of therapy were eligible to be rechallenged at time of DP. Clinical outcomes analyzed were best overall response, duration of response, disease control rate (DCR), and progression-free survival (PFS), defined as time from first day of retreatment with durvalumab to DP or death.
Of 1,022 patients, 160 stopped durvalumab without developing DP after 1 year of treatment. Of those, 70 (43.8%) patients across 14 different primary tumor types were rechallenged with durvalumab after DP (Table). During their first treatment with durvalumab, 5.7% and 50% had achieved complete responses (CR) and partial responses (PR), respectively. While off therapy, median time without DP was 266 days. After rechallenge with durvalumab, 66 of 70 (94.3%) were evaluable. Confirmed best overall response was 0% CR, and 11.4% had PR, 60% had stable disease (SD), and 22.9% had DP. Median duration of response was 16.5 months. DCR at ≥ 24 weeks was 47.1%. PFS at 12 months was 34.2%, with similar rates observed regardless of tumor type. 1175O Best overall response and 12-month PFS with durvalumab rechallengeTumour Type All Patients (N = 70) NSCLC (n = 21) MSI-High (n = 12) Bladder (n = 8) HNSCC (n = 6) HCC (n = 5) Other (n = 18) Best overall response, n (%) CR 0 0 0 0 0 0 0 PR 8 (11.4) 3 (14.3) 0 3 (37.5) 0 1 (20.0) 1 (5.6) SD 42 (60) 8 (38.1) 11 (91.7) 3 (37.5) 4 (66.7) 4 (80.0)12 12 (66.7) DP 16 (22.9) 8 (38.1) 1 (8.3) 2 (25.0) 2 (33.3) 0 3 (16.7) Nonevaluable 4 (5.7) 2 (9.5) 0 0 0 0 2 (11.1) Duration of response, months 16.5 13.4 N/A 16.5 N/A 18.7+ 12+ CR/PR + SD (DCR ≥24 weeks), % 47.1 33.3 58.3 50.0 33.3 40.0 40.0 PFS at 12 months, % 34.2 31 59.4 62.5 20 25 72.2
This is the largest cohort supporting the role of rechallenge with a PD-1/PD-L1 inhibitor in patients who have previously progressed after planned interruption. Rechallenge with durvalumab resulted in restored antitumor efficacy, high rates of disease control, and prolonged durability in patients who responded. These findings support the role of durvalumab in patients who progressed after planned treatment interruption.
NCT01693562.
AstraZeneca, PLC.
AstraZeneca.
S. Sheth: Research grant / Funding (institution): AstraZeneca. C. Gao: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. N. Mueller: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Martinez: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Soria: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca.