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Alexander Spira
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.16-06 - Expanded Efficacy and Safety Analysis of PACIFIC Based on a PD-L1 Cutpoint of 25% (ID 12992)
16:45 - 18:00 | Presenting Author(s): Alexander Spira
- Abstract
Background
In the Phase 3 PACIFIC study of patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT), PFS was significantly longer with durvalumab versus placebo (stratified HR 0.52; 95% CI 0.42–0.65; P<0.0001). We report exploratory analyses of PACIFIC outcomes by PD-L1 expression assessed in tumor samples collected prior to cCRT.
a9ded1e5ce5d75814730bb4caaf49419 Method
PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind study of patients with WHO PS 0/1 without progression after ≥2 cycles of platinum-based cCRT. Eligibility was irrespective of PD-L1 expression; archived samples were optional for testing (VENTANA PD-L1 [SP263] assay). No samples were obtained after cCRT, prior to infusion with durvalumab or placebo. Patients were randomized (2:1) to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex and smoking history. Co-primary endpoints were PFS (blinded independent central review, RECIST v1.1) and OS (not available). Secondary endpoints included ORR and safety. We investigated associations between subgroups of patients with PD-L1 expression on tumor cells (TC) of <25% or ≥25% and efficacy.
4c3880bb027f159e801041b1021e88e8 Result
As of February 13, 2017, 713 patients were randomized; 451 (63.3%) had known PD-L1 status (TC<25%, 64.7%; TC≥25%, 35.3%; Table). Baseline characteristics and prior therapy (including best response to prior therapy) were generally well balanced between arms across both PD-L1 subgroups. PFS benefit with durvalumab was demonstrated irrespective of PD-L1 status (HR 0.59; 95% CI, 0.43–0.82 for TC<25% and HR 0.41; 95% CI, 0.26–0.65 for TC≥25%) (Table). ORR was greater with durvalumab compared to placebo regardless of PD-L1 status (Table). The overall safety profile of durvalumab in each PD-L1 subgroup was consistent with the ITT population treated with durvalumab.
8eea62084ca7e541d918e823422bd82e Conclusion
Durvalumab demonstrated clinical benefit and had a well-tolerated, manageable safety profile irrespective of PD-L1 status obtained from archival tumor samples prior to cCRT.
6f8b794f3246b0c1e1780bb4d4d5dc53PD-L1 TC<25%
PD-L1 TC≥25%
Durvalumab (n=187)
Placebo
(n=105)Durvalumab (n=115)
Placebo
(n=44)Completed 12 months treatment, n (%)
74 (39.6)
35 (33.3)
55 (47.8)
13 (29.5)
PFS*
Median (95% CI), months
16.9 (11.0–NR)
6.9 (5.0–11.0)
17.8 (11.1–NR)
3.7 (2.0–13.2)
HR (95% CI)
0.59 (0.43–0.82)
0.41 (0.26–0.65)
ORR†
n=170
n=96
n=108
n=40
n (%)
[95% CI]
50 (29.4)
[22.7–36.9]
19 (19.8)
[12.36–29.17]
31 (28.7)
[20.4–38.2]
6 (15.0)
[5.71–29.84]
*In the overall ITT population, median PFS was 16.8 months (95% CI, 13.0–18.1) with durvalumab (n=476) vs. 5.6 months (95% CI, 4.6–7.8) with placebo (n=237), with an HR of 0.52 (95% CI, 0.42–0.65; P<0.001) (stratified log-rank); PD-L1 assessment was not required in the study; in PD-L1 unknown patients, median PFS was 14.0 months (95% CI, 9.2–NR) with durvalumab (n=174) vs. 6.4 months (95% CI, 3.8–9.0) with placebo (n=88), with an HR of 0.59 (95% CI, 0.42–0.83) (unstratified Cox proportional hazards model); †ORR for n evaluable patients included unconfirmed responses. ITT, intention-to-treat; NR, not reached; ORR, objective response rate; PFS, progression-free survival.
