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Johan F. Vansteenkiste



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    LA01 - IASLC Lectureship Award Session (ID 989)

    • Event: WCLC 2018
    • Type: Lectureship Award Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 105
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      LA01.01 - Clifton F. Mountain Lectureship Award for Staging - Is There Still a Stage for Improvements in Staging? (ID 14697)

      13:30 - 13:40  |  Presenting Author(s): Johan F. Vansteenkiste

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MA02 - Improving Outcomes for Patients with Lung Cancer (ID 895)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 201 BD
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      MA02.03 - ASTRIS: A Real World Treatment Study of Osimertinib in Patients with EGFR T790M-Positive NSCLC (ID 12972)

      10:40 - 10:45  |  Author(s): Johan F. Vansteenkiste

      • Abstract
      • Presentation
      • Slides

      Background

      Osimertinib is a third-generation, CNS-active EGFR-TKI that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations. We report results from a second planned protocol, optimal interim analysis of the ongoing ASTRIS study (NCT02474355).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eligible patients receive osimertinib 80 mg once daily. Inclusion criteria: stage IIIB/IV T790M-positive non-small cell lung cancer (NSCLC); T790M status confirmed locally by validated test, not restricted by sample type; prior EGFR-TKI therapy received; WHO performance status (PS) 0−2; acceptable organ and bone marrow function and no history of interstitial lung disease (ILD) or QTc prolongation. Asymptomatic, stable CNS metastases are permitted. The primary efficacy outcome is overall survival (OS).

      4c3880bb027f159e801041b1021e88e8 Result

      From Sept 18, 2015, first patient in, to Oct 20 2017 data cut-off (DCO), 3014 patients were enrolled across 16 countries and received ≥1 dose of osimertinib (full analysis set [FAS]): median follow-up 7.9 months (range <1−24), median age 62 yrs (27–92), 64% female, 69% Asian, 30% White, 11% WHO PS 2, 45% prior chemotherapy, 34% prior radiotherapy. All patients had T790M-positive status, identified from tissue in 1610 patients (53%), plasma ctDNA in 1241 patients (41%) and from other sources in 162 patients (5%). At DCO, 1276 patients (42%) had discontinued treatment (1738 [58%] ongoing); median duration of exposure 7.4 months (<1–25); 1289 patients (43%) had a progression-free survival (PFS) event, 1276 (42%) had a time to treatment discontinuation (TTD) event, and 593 (20%) had died. In patients evaluable for response, the investigator-assessed clinical response rate was 56.6% (1625/2872; 95% confidence interval [CI] 54.7, 58.4). In the FAS, estimated median PFS was 11.0 months (95% CI 10.6, 11.1), median TTD was 12.6 months (95% CI 12.2, 13.7), and median OS was not reached (OS at 12 months was 75.8% (95% CI 73.7, 77.8). Adverse events (AEs) leading to dose modification and treatment discontinuation were reported in 321 patients (11%) and 147 patients (5%), respectively. Serious AEs were reported in 505 patients (17%). ILD/pneumonitis-like events were reported in 41 patients (1%), and QTc prolongation in 48 patients (2%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      ASTRIS, the largest reported study of osimertinib in T790M-positive NSCLC, demonstrates clinical activity similar to that observed in the osimertinib clinical trial program with no new safety signals.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MA05 - Improving Outcomes in Locoregional NSCLC II (ID 901)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 105
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      MA05.02 - PACIFIC Subgroup Analysis: Pneumonitis in Stage III, Unresectable NSCLC Patients Treated with Durvalumab vs. Placebo After CRT (ID 13876)

      13:35 - 13:40  |  Presenting Author(s): Johan F. Vansteenkiste

      • Abstract
      • Presentation
      • Slides

      Background

      In the Phase 3 PACIFIC study of durvalumab versus placebo in patients with stage III, unresectable non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (cCRT), on-treatment pneumonitis or radiation pneumonitis (‘pneumonitis’) occurred in both arms with similar rates of grade 3/4 pneumonitis (durvalumab, 3.4%; placebo, 2.6%). We performed exploratory analyses to further characterize time to onset and duration of pneumonitis and examine its relationship with underlying risk factors, including patient characteristics and prior CRT.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PACIFIC (NCT02125461) was a randomized, double-blind study of patients with WHO PS 0/1 without progression after ≥2 cycles of platinum-based cCRT. Patients were stratified by age, sex, and smoking history and randomized (2:1) 1–42 days after completing cCRT to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Potential associations between the presence of the AE pneumonitis (investigator assessed with review/adjudication by study sponsor) and baseline characteristics or patient disposition were investigated.

      4c3880bb027f159e801041b1021e88e8 Result

      As of Feb 13, 2017, 709 patients had received treatment; 33.6% on durvalumab and 24.9% on placebo had any-grade pneumonitis. Treatment exposure was similar in patients with or without pneumonitis across both arms. Median time to onset of pneumonitis from treatment start was the same for both durvalumab and placebo, 55.0 days (73.0 and 76.5 days from RT completion). Pneumonitis was self-limited, with median durations of 64.0 and 57.0 days, respectively. Patients with pneumonitis were more likely to be Asian (47.9% vs 17.6%) or have EGFR mutations (11.0% vs 3.8%); however, the proportions of patients with pneumonitis and these risk factors were numerically lower with durvalumab than with placebo (Asian: 44.4% [71/160] vs 57.6% [34/59]; EGFRm: 10.6% [17/160] vs 11.9% [7/59]), suggesting no apparent interaction with treatment. There were no apparent associations of pneumonitis with baseline respiratory disorders, prior RT dose, or prior cisplatin or carboplatin use. Previous induction CT was more commonly associated with the absence of pneumonitis in both treatment arms (durvalumab: 30.1% vs 17.5%; placebo: 31.5% vs 20.3%). The presence of pneumonitis was associated with greater discontinuation due to AEs (durvalumab: 25.6% vs 10.2%; placebo: 18.6% vs 6.8%) regardless of treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Rates of pneumonitis were higher in Asian patients and those with EGFRm, as previously reported. Durvalumab did not increase pneumonitis in patients with these risk factors. There were no differences in treatment exposure in patients based on the presence/absence of pneumonitis. Multivariate analyses may further assist in the discernment of etiologic risks.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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      MA15.03 - PD-L1 Expression in Untreated EGFRm Advanced NSCLC and Response to Osimertinib and SoC EGFR-TKIs in the FLAURA Trial (ID 12989)

      13:40 - 13:45  |  Author(s): Johan F. Vansteenkiste

      • Abstract
      • Presentation
      • Slides

      Background

      In the Phase III FLAURA trial (NCT02296125), osimertinib significantly improved PFS relative to SoC EGFR-TKIs (gefitinib/erlotinib) in patients with untreated Ex19del/L858R positive (EGFRm) NSCLC. EGFRm NSCLC tumors can exhibit high PD-L1 expression, an important biomarker for immunotherapy treatment decisions. The frequency and clinical relevance of exhibiting both biomarkers prior to treatment are unclear. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following EGFR-TKI treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tissue samples from 994 patients with advanced NSCLC were screened for EGFR Ex19del/L858R mutations for enrolment in FLAURA; 556 were randomized to treatment. 197 tissue-blocks from the screened population (including EGFR mutation-positive and -negative samples) were tested for PD-L1 using the SP263 (Ventana) immunohistochemical assay; positive tumour cell (TC) staining PD-L1 TC≥25% and TC≥1% thresholds were applied. PFS was investigator-assessed, per RECIST 1.1, according to PD-L1-expressers (TC≥1%) or -negatives (TC<1%) in randomized patients.

      4c3880bb027f159e801041b1021e88e8 Result

      193/197 blocks had sufficient tumor tissue for staining. 65/193 patients were EGFR mutation-negative. 128/193 patients were EGFR mutation-positive: 106/128 were randomized to treatment (osimertinib: 54; SoC: 52). The table presents PD-L1 expression according to EGFR mutation status. For PD-L1-expressers (TC≥1%), median PFS was 18.4 months for osimertinib and 6.9 months for SoC (HR 0.30 [95% CI 0.15, 0.60]). For PD-L1-negative patients (TC<1%), median PFS was 18.9 months for osimertinib and 10.9 months for SoC (HR 0.37 [95% CI 0.17, 0.74]).

      PD-L1 TC≥1%, n (%)

      PD-L1 TC≥25%, n (%)

      EGFR mutation-negative (n=65)

      Screened population (n=65)

      44 (68)

      23 (35)

      EGFR mutation-positive (n=128)

      Screened population (n=128)

      65 (51)

      10 (8)

      Randomized to treatment (n=106)

      52 (49)

      8 (8)

      Randomized to osimertinib (n=54)

      28 (52)

      3 (6)

      Randomized to SoC EGFR-TKI (n=52)

      24 (46)

      5 (10)

      8eea62084ca7e541d918e823422bd82e Conclusion

      There was PFS benefit with osimertinib versus SoC regardless of whether tumors were PD-L1-expressers (TC≥1%) or -negatives (TC<1%). Using the TC≥25% threshold, PD-L1 prevalence was lower in EGFR mutation-positive than mutation-negative samples; there were insufficient patients with TC≥25% tumors for PFS assessment.

      These results support the efficacy of EGFR-TKIs, including osimertinib, as first-line treatment of EGFRm advanced NSCLC, irrespective of PD-L1 expression.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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      MA25.03 - Defining Oligometastatic Non-Small Cell Lung Cancer (NSCLC): An Evolving Multidisciplinary Expert Opinion (ID 12573)

      13:35 - 13:40  |  Author(s): Johan F. Vansteenkiste

      • Abstract
      • Presentation
      • Slides

      Background

      Synchronous oligometastatic NSCLC definition varies between: 1 metastasis in 1 organ (TNM8), 1-3 metastases (ESMO), ≤3 metastases after systemic treatment with mediastinal nodes (MLN) counting as 1 site (Gomez, Lancet Oncol 2016) to 3-≥5 metastases in ongoing trials. A single definition is however needed to design and compare trials. To assess synchronous oligometastatic NSCLC definitions used by clinical experts in daily practice and its evolution, we redistributed a 2012-case based survey (Dooms et al, presented at WCLC 2013).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In December 2017, 10 real-life multidisciplinary team (MDT) discussed patients (all good condition, no significant comorbidities, 18FFDG-PET and brain MRI staged, all < 5 metastases, 9/10 ≤ 3 metastases, oncogene-addicted or wildtype NSCLC) were distributed to 33 international NSCLC experts involved in the EORTC oligometastatic NSCLC consensus group, questioning: 1) can you discuss these cases in your MDT?, 2) do these patients have oligometastatic disease? and 3) what is your treatment proposal for the oligometastatic disease patients? Current answers were compared to the previous ones, and the real-life treatment and survival of the patients was added.

      4c3880bb027f159e801041b1021e88e8 Result

      26/33 experts (24 centers) replied: 8 medical oncologists, 7 pulmonologists, 7 radiation oncologists, 4 thoracic surgeons. 62% discussed the cases in their MDT. 1 case had 100% oligometastatic disease consensus, 3 cases had > 90% consensus, the number of treatment proposals varied between 3 to 8 (Table). Radical treatment was more often offered in case of a single metastasis or N0 status. Compared to 2012 there was a trend towards a more conservative oligometastatic definition and chemotherapy was more often included in the treatment proposal.

      table 1
      Case TNM8

      oligometastatic

      yes answer %

      2012 / 2017

      Number of tx

      proposals

      2012 / 2017

      Radical tx

      answers %

      2012/2017

      Real life radical

      tx intent

      real life survival

      (months) /

      5Y survival

      EGFR+ T2aN3M1c (3 brain mets) 55 / 38 2 / 5 27 / 23 - 40.1 / -
      EGFR+ T4N0M1a (ground glass) 36 / 35 4 / 3 45 / 35 + 65.2 / +
      T2aN1M1b (solitary renal) 91 / 96 5 / 5 100 / 92 + 8.3 / -
      T1bN3M1b (solitary adrenal) 73 / 58 4 / 5 36 / 54 + 66.1 / +
      T2bN1M1c (adrenal + pelvic node) 55 / 50 2 / 5 36 / 46 - 18.6 / -
      T2aN0M1c (3 liver mets) 64 / 69 4/ 5 27 / 62 - 51.5 / -
      T2aN2M1b (solitary bone) 91 / 92 4 / 5 73 / 85 + 13.4 / -
      T3N1M1c (2 brain mets) 91 / 96 3 / 8 73 / 85 + 39.6 / -
      T2aN0M1c (1 lung, 1 pancreas) 82 / 69 5 / 4 64 / 50 + 74.0 / +
      T1bN0M1b (solitary bone) 100 / 100 3 / 5 82 / 92 + 11.6 / -

      8eea62084ca7e541d918e823422bd82e Conclusion

      Synchronous oligometastatic NSCLC definition was more conservative than in 2012 and linked to radical intent of treatment. Number of organs, MLN status and possibility for radical treatment seem to be components of daily practice synchronous oligometastatic definition.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MS14 - IO in Early Stage NSCLC (ID 793)

    • Event: WCLC 2018
    • Type: Mini Symposium
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 107
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      MS14.01 - Basic Science Rationale of IO in Early Stage NSCLC? (ID 11458)

      10:30 - 10:45  |  Presenting Author(s): Johan F. Vansteenkiste

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    OA05 - Clinical Trials in IO (ID 899)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
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      OA05.05 - Avelumab vs Docetaxel for Previously Treated Advanced NSCLC: Primary Analysis of the Phase 3 JAVELIN Lung 200 Trial (ID 12930)

      14:15 - 14:25  |  Author(s): Johan F. Vansteenkiste

      • Abstract
      • Presentation
      • Slides

      Background

      Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody that is an approved treatment for metastatic Merkel cell carcinoma (various regions) and platinum-treated advanced urothelial carcinoma (US). We report findings from a global, open-label, phase 3 trial of avelumab vs docetaxel in patients with advanced NSCLC after platinum failure (NCT02395172).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with stage IIIB/IV or recurrent NSCLC with disease progression after platinum doublet therapy were randomized 1:1 to avelumab 10 mg/kg Q2W or docetaxel 75 mg/m2 Q3W, stratified by PD-L1 status (PD-L1+/PD-L1−) and histology (squamous/nonsquamous). The primary endpoint was overall survival (OS) in the PD-L1+ population (expression on ≥1% of tumor cells, assessed using the PD-L1 IHC 73-10 assay).

      4c3880bb027f159e801041b1021e88e8 Result

      Between April 2015 and February 2017, 792 patients were randomized to receive avelumab or docetaxel, including 264 and 265 with PD-L1+ tumors, respectively; 0.8% vs 7.5% did not receive study treatment. Median follow-up in the avelumab and docetaxel arms was 18.9 and 17.8 months; 15.5% vs 1.5% remained on treatment at data cutoff (November 22, 2017). In the avelumab and docetaxel arms, 39.8% vs 47.5% received subsequent anticancer therapy after discontinuation, including checkpoint inhibitors in 5.7% vs 26.4%, respectively. In the PD-L1+ population, median OS in the avelumab and docetaxel arms was 11.4 vs 10.3 months (hazard ratio [HR], 0.90 [96% CI, 0.72-1.12]; P=0.1627, 1-sided). Pre-planned exploratory analyses based on higher PD-L1 cutoffs showed increased OS with avelumab vs docetaxel, including PD-L1-high (≥80% cutoff, 29% of patients; 17.1 vs 9.3 months; HR, 0.59 [95% CI, 0.42-0.83]; P=.0022, 2-sided) and PD-L1-medium/high (≥50% cutoff, 40% of patients; 13.6 vs 9.2 months; HR, 0.67 [95% CI, 0.51-0.89]; P=0.0052, 2-sided) subgroups. In the PD-L1+ population (≥1% cutoff), ORR was 18.9% vs 11.7% (odds ratio, 1.76 [95% CI, 1.08-2.86]; P=0.0105, 1-sided); median duration of response was not reached with avelumab (95% CI, 9.9-not estimable [NE]) vs 6.9 months with docetaxel (95% CI, 3.5-NE). Overall rates of treatment-related adverse events (AEs) were lower with avelumab than docetaxel, including all grades (63.9% vs 85.8%) and grade ≥3 (9.9% vs 49.3%). Immune-related AEs occurred in 16.5% of avelumab-treated patients (grade ≥3 in 2.8%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Avelumab showed increasing clinical activity in patients who had platinum-treated NSCLC with higher tumor PD-L1 expression; however, the trial did not meet its primary objective of improving OS vs docetaxel in PD-L1+ tumors (≥1% cutoff). OS findings may have been confounded by subsequent checkpoint inhibitor therapy in the docetaxel arm.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • 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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      P1.01-21 - Safety of Durvalumab Retreatment in Advanced NSCLC Patients Who Progressed Following Initial Disease Control In ATLANTIC (ID 12386)

      16:45 - 18:00  |  Author(s): Johan F. Vansteenkiste

      • Abstract
      • Slides

      Background

      In ATLANTIC, patients who completed a year of durvalumab (anti-PD-L1) treatment but later progressed off therapy were eligible for retreatment. We evaluated safety in these patients compared with the overall study population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      ATLANTIC (NCT02087423) was a Phase 2, open-label, single-arm trial in patients with Stage IIIB–IV NSCLC who had received ≥2 prior systemic treatment regimens, including one platinum-based. The study included three independent cohorts. In C1 (EGFR+/ALK+) and C2 (EGFR−/ALK−), enrollment was enriched for patients with ≥25% of tumor cells (TC) expressing PD-L1, while patients in C3 (EGFR−/ALK−) only had PD-L1 TC ≥90%. Patients received durvalumab 10 mg/kg q2w for ≤12 months. Patients who achieved and maintained disease control but then progressed after completing the initial 12-month treatment period were offered retreatment for a maximum of 12 months of further treatment. Safety and tolerability was a secondary outcome.

      4c3880bb027f159e801041b1021e88e8 Result

      As of November 7, 2017, of 442 patients in the ATLANTIC full analysis set, 102 (23.1%) had completed 12 months of initial treatment and 95 (21.5%) had disease control at the end of initial treatment. A total of 40 patients started retreatment. The median actual duration of exposure to durvalumab was 16.0 weeks (range 1–62; 40.1% of patients on treatment for ≥24 weeks) during initial treatment and 18.1 weeks (range 2–52; 37.5% of patients on retreatment for ≥24 weeks) during retreatment. The table shows safety during initial treatment and retreatment.

      Initial treatment (n=444)

      Retreatment phase (n=40)

      Cohort,* n (%)

      C1 (EGFR+/ALK+)

      111 (25.0)

      7 (17.5)

      C2 (EGFR−/ALK−)

      265 (59.7)

      26 (65.0)

      C3 (EGFR−/ALK−; TC ≥90%)

      68 (15.3)

      7 (17.5)

      Any TRAE, n (%)

      256 (57.7)

      19 (47.5)

      Grade ≥3 TRAEs

      42 (9.5)

      6 (15.0)

      TRAEs leading to death

      0

      2 (5.0)

      Serious TRAEs

      28 (6.3)

      4 (10.0)

      TRAEs leading to discontinuation

      10 (2.3)

      4 (10.0)

      Safety analysis set. *A more detailed analysis of exposure and safety by cohort will be presented. Causes of death were: pneumonitis and respiratory failure; cardiac arrest. TRAE=treatment-related adverse event.

      8eea62084ca7e541d918e823422bd82e Conclusion

      A large proportion of patients (37.5%) maintained retreatment for ≥24 weeks, suggesting that patients who originally completed 12 months of treatment can tolerate sustained retreatment. The tolerability profile of durvalumab upon retreatment was similar to that seen during initial treatment, although there were two treatment-related deaths during the retreatment phase. Retreatment with anti-PD-L1 may be feasible for selected patients with NSCLC who demonstrate original benefit and progress off therapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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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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      P1.16-05 - Effect of Induction Chemotherapy in the PACIFIC Study (ID 13864)

      16:45 - 18:00  |  Author(s): Johan F. Vansteenkiste

      • Abstract
      • Slides

      Background

      The Phase 3 PACIFIC study of patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT) demonstrated significantly longer PFS with durvalumab versus placebo (stratified HR 0.52; 95% CI 0.42–0.65; P<0.0001). Overall, 26% and 29% in the durvalumab and placebo groups, respectively, received induction chemotherapy (ICT) before cCRT. Here, we report exploratory analyses of baseline characteristics, disposition, and outcomes from this study based on the presence or absence of prior ICT.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind study of patients with WHO PS 0/1 and any tumor PD-L1 status without progression after ≥2 cycles of platinum-based cCRT. Patients were stratified by age, sex and smoking history and randomized (2:1) to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Co-primary endpoints were PFS (blinded independent central review, RECIST v1.1) and overall survival (not available). We investigated associations between the presence/absence of ICT and disposition, baseline characteristics, and efficacy and safety endpoints.

      4c3880bb027f159e801041b1021e88e8 Result

      As of February 13, 2017, 713 patients were randomized; 27% had prior ICT. Baseline characteristics were similar between treatment arms; however, patients with ICT were generally younger, less frequently Asian, had lower incidence of squamous histology, and more often had stage IIIB disease. There were no differences between groups in terms of prior RT dose. PFS benefit with durvalumab was demonstrated irrespective of ICT use (ICT: HR=0.61, 95% CI, 0.41–0.88; no ICT: HR=0.54, 95% CI, 0.42–0.69). Similarly, ORR with durvalumab was numerically higher than with placebo irrespective of ICT use (ICT: 16.1% vs 13.1%; no ICT: 32.9% vs 17.1%). ICT did not affect treatment duration for durvalumab or placebo. Between-treatment safety differences were minimal across subgroups; however, patients with ICT experienced fewer SAEs, treatment-related SAEs and pneumonitis/radiation pneumonitis regardless of treatment arm.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Durvalumab demonstrated clinical benefit irrespective of ICT. The safety profile of durvalumab was consistent in patients with or without ICT. A lower rate of toxicity was observed in patients with ICT regardless of treatment arm.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)

    • Event: WCLC 2018
    • Type: Plenary Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
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      PL02.01 - Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC (ID 14701)

      08:15 - 08:25  |  Author(s): Johan F. Vansteenkiste

      • Abstract
      • Presentation
      • Slides

      Background

      In the global, Phase 3 PACIFIC study (Antonia 2017; NCT02125461), durvalumab significantly improved progression-free survival (PFS) versus placebo in Stage III, unresectable NSCLC patients without progression after chemoradiotherapy (CRT) (stratified HR, 0.52; 95% CI, 0.42–0.65; P<0.001). This was the first major advance in this disease setting for many years. Here we report the second primary endpoint overall survival (OS) for PACIFIC.

      Patients with WHO PS 0/1 (any PD-L1 tumor status) who received ≥2 cycles of platinum-based CRT were randomized (2:1) 1–42 days post-CRT to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex, and smoking history. Primary endpoints were PFS from randomization (blinded independent central review; RECIST v1.1) and OS (interim analysis reported). Secondary endpoints included time to death or distant metastasis (TTDM) and PFS2 (time to second progression) from randomization and safety. Time to first/second subsequent therapy or death (TFST/TSST) were supportive assessments for PFS/PFS2.

      Between May 2014 and April 2016, 713 patients were randomized of whom 709 received treatment (durvalumab, n=473; placebo, n=236). As of March 22, 2018 (data cutoff), median follow-up duration was 25.2 months (range, 0.2–43.1). After discontinuation, 41.0% and 54.0% in the durvalumab and placebo groups received subsequent anticancer therapy; overall, 8.0% and 22.4% received additional immunotherapy. Durvalumab significantly improved OS versus placebo (stratified HR 0.68, 99.73% CI, 0.469–0.997; P=0.00251), with the median not reached (NR; 95% CI, 34.7 months–NR) and 28.7 months (95% CI, 22.9–NR), respectively. Durvalumab improved OS in all pre-specified subgroups. Updated PFS remained similar (stratified HR 0.51, 95% CI, 0.41–0.63), with medians of 17.2 and 5.6 months with durvalumab and placebo, respectively. Durvalumab improved the updated TTDM (stratified HR 0.53, 95% CI, 0.41–0.68), as well as PFS2 (stratified HR 0.58, 95% CI, 0.46–0.73), TFST (stratified HR 0.58, 95% CI, 0.47–0.72) and TSST (stratified HR 0.63, 95% CI, 0.50–0.79). Within the durvalumab and placebo groups, 30.5% and 26.1% had grade 3/4 any-causality AEs, 15.4% and 9.8% discontinued due to AEs, and no new safety signals were identified.

      Durvalumab demonstrated statistically significant and clinically meaningful improvement in OS compared with placebo, supported by secondary endpoints such as PFS2. PACIFIC is the first study to show a survival advantage following CRT in this population, providing compelling evidence for the unprecedented benefit of durvalumab treatment as the standard of care.

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