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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
      • Slides


      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.

      PD-L1 TC<25%

      PD-L1 TC≥25%

      Durvalumab (n=187)


      Durvalumab (n=115)


      Completed 12 months treatment, n (%)

      74 (39.6)

      35 (33.3)

      55 (47.8)

      13 (29.5)


      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)






      n (%)

      [95% CI]

      50 (29.4)


      19 (19.8)


      31 (28.7)


      6 (15.0)


      *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.


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