Virtual Library

Start Your Search

Rina Hui



Author of

  • +

    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
    • +

      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  |  Author(s): Rina Hui

      • 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

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA10 - Considerations in Immunotherapy / Real World (ID 911)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 105
    • +

      MA10.08 - Choice of Taxane and Outcomes in the KEYNOTE-407 Study of Pembrolizumab Plus Chemotherapy for Metastatic Squamous NSCLC (ID 14698)

      11:25 - 11:30  |  Author(s): Rina Hui

      • Abstract
      • Presentation
      • Slides

      Background

      In the randomized, double-blind, phase 3 KEYNOTE-407 study (NCT02775435), pembrolizumab plus chemotherapy with carboplatin and paclitaxel or nab-paclitaxel significantly prolonged OS (HR 0.64, 95% CI 0.49-0.85, P=0.0008) and PFS (HR 0.56, 95% CI 0.45-0.70, P<0.0001) compared with placebo plus chemotherapy in patients with previously untreated, metastatic squamous NSCLC. The benefit of pembrolizumab plus chemotherapy was observed irrespective of PD-L1 TPS. Pembrolizumab plus chemotherapy also had a manageable safety profile. We performed an exploratory analysis of outcomes by investigator’s choice of paclitaxel or nab-paclitaxel, which was a randomization stratification factor.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      559 eligible patients were randomized 1:1 to pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus 4 cycles of carboplatin AUC 6 mg/mL/min Q3W and investigator’s choice of paclitaxel 200 mg/m2 Q3W or nab-paclitaxel 100 mg/m2 QW. Primary end points were OS and PFS; ORR and safety were secondary.

      4c3880bb027f159e801041b1021e88e8 Result

      Paclitaxel was the chosen taxane in 60% of patients. The addition of pembrolizumab to chemotherapy improved OS, PFS, and ORR regardless of choice of carboplatin and paclitaxel or carboplatin and nab-paclitaxel (Table). Incidence of grade 3-5 AEs in the pembrolizumab plus chemotherapy arm vs placebo plus chemotherapy arm was 63.9% vs 59.3% in paclitaxel recipients and 78.9% vs 81.4% in nab-paclitaxel recipients. AEs led to discontinuation of all treatment in 13.6% vs 8.4% of paclitaxel recipients and 12.8% vs 3.5% of nab-paclitaxel recipients and led to discontinuation of any treatment in 19.5% vs 13.2% and 29.4% vs 9.7%, respectively. Immune-mediated AEs occurred in 29.6% vs 9.6% of paclitaxel recipients and 27.5% vs 7.1% of nab-paclitaxel recipients.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Adding pembrolizumab to chemotherapy with carboplatin and a taxane improved efficacy and was generally tolerable compared with chemotherapy alone as first-line therapy in patients with metastatic squamous NSCLC regardless of whether paclitaxel or nab-paclitaxel was the chosen taxane.

      Carboplatin plus Paclitaxel Carboplatin plus Nab-Paclitaxel

      Pembrolizumab + Chemotherapy

      N = 169

      Placebo + Chemotherapy

      N = 167

      Pembrolizumab + Chemotherapy

      N = 109

      Placebo + Chemotherapy

      N = 114

      OS, median

      (95% CI), mo

      14.0 (12.6-16.6) 10.3 (8.2-14.8) NR (NE-NE) 12.6 (9.6-NE)
      HR (95% CI)a 0.67 (0.48-0.93) 0.59 (0.36-0.98)

      PFS, median

      (95% CI), mo

      6.4 (6.0-8.3) 4.4 (4.2-5.1) 6.5 (6.2-8.5) 5.9 (4.4-6.9)
      HR (95% CI)a 0.52 (0.40-0.68) 0.65 (0.45-0.94)
      ORR, % (95% CI) 57.4 (49.6-65.0) 37.7 (30.4-45.5) 58.7 (48.9-68.1) 39.5 (30.4-49.1)
      aBased on a Cox regression model with treatment as a covariate.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    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
    • +

      P1.01-81 - Phase 3 Study of Pemetrexed-Platinum with or without Pembrolizumab for TKI-Resistant/EGFR-Mutated Advanced NSCLC: KEYNOTE-789 (ID 14192)

      16:45 - 18:00  |  Author(s): Rina Hui

      • Abstract
      • Slides

      Background

      In the phase 3 KEYNOTE-189 study, pembrolizumab plus pemetrexed-platinum improved OS and PFS over chemotherapy plus placebo in first-line, metastatic NSCLC without targetable EGFR mutations (Gandhi et al. NEJM 2018). The phase 3 KEYNOTE-789 (ClinicalTrials.gov, NCT03515837) study evaluates pemetrexed-platinum combined with pembrolizumab vs placebo in EGFR-TKI–resistant, EGFR-mutated, metastatic nonsquamous NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eligibility for this multicenter, randomized, double-blind, placebo-controlled study requires age ≥18 years; EGFR-TKI–resistant EGFR-mutated (exon 19 deletion or L858R mutation), histologically/cytologically confirmed stage IV, nonsquamous NSCLC; measurable disease per RECIST version 1.1; ECOG PS 0/1; and archival/newly obtained pretreatment tumor sample to evaluate PD-L1 expression. If progression on prior EGFR-TKI occurred with first- or second-generation TKIs (eg, erlotinib, afatinib, gefitinib) and T790M mutation is present, patients must have had subsequent progression on osimertinib; patients with progression on first-line osimertinib are eligible regardless of EGFR T790M mutation status. Patients are randomized 1:1 to pembrolizumab 200 mg or placebo, each in combination with pemetrexed 500 mg/m2 plus platinum chemotherapy (carboplatin AUC 5 or cisplatin 75 mg/m2; investigator’s choice) Q3W for 4 cycles. Patients continue allocated treatment (pembrolizumab or placebo) plus pemetrexed for up to 35 cycles, followed by pemetrexed maintenance therapy until documented disease progression or intolerable toxicity. Randomization is stratified by PD-L1 tumor proportion score ≥50% vs <50%, prior osimertinib vs no prior osimertinib, and geographic region of East Asia vs non-East Asia. Tumor response is assessed radiographically at baseline, week-6, then every 9 weeks through week-54 and every 12 weeks thereafter, per RECIST version 1.1 by blinded, independent central review. Treatment decisions are based on iRECIST criteria by investigator review. PFS and OS are dual primary endpoints, which will be tested with one-sided alphas of 0.001 and 0.02, respectively. Secondary endpoints are ORR; duration of response; change from baseline global health status and quality-of-life scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30; time to true deterioration in composite endpoint of cough, chest pain, or dyspnea on EORTC QLQ-Lung Cancer Module 13; and safety and tolerability. Severity of AEs will be graded per NCI CTCAE version 4.0. Approximately 480 patients will be enrolled beginning June 1, 2018.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.04-11 - Exploring the Germ-Line Contribution to Exceptional Response to PD-1/PD-L1 Inhibition in Patients with NSCLC by Whole Genome Sequencing (ID 12646)

      16:45 - 18:00  |  Author(s): Rina Hui

      • Abstract
      • Slides

      Background

      Responses to immune checkpoint inhibitors (CPI) may vary between individuals because of somatic mutation differences in the tumour and/or germ-line differences in immunological tolerance. To explore the latter, this ongoing study evaluates patients with metastatic non-small cell lung cancer (NSCLC) treated with single agent PD-1 or PD-L1 inhibitors recruited from a treatment pool of 420 patients (total) / 137 (active since 1 August 2017).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Rare and common germ-line DNA variants are analysed in exceptional responders and non-responders by whole genome sequencing (WGS) (Illumina HiSeqX Ten). Exceptional responders are defined as patients with complete or partial response of more than 12 months or stable disease of more than 24 months (per RECIST), and a concurrent immune-related adverse event of any grade. Non-responders are defined as patients with best response of progressive disease, having received at least 4 cycles or 2 months of treatment.

      In these individuals, the burden of rare and common variants in immune tolerance genes is analysed and compared to the Medical Genome Reference Bank (MGRB), comprising WGS of 1144 well-elderly individuals. Comparisons are made with Fisher Exact test. Genetic risk scores for auto-immune conditions are calculated for these cohorts, MGRB and NSCLC patients included in The Cancer Genome Atlas. Scores are calculated using curated risk alleles and OR weightings derived from the NHGRI-EBI GWAS catalogue.

      4c3880bb027f159e801041b1021e88e8 Result

      Recurrent rare variants (Exome Aggregation Consortium (ExAC) frequency < 1%) were found within responders sequenced to date (n=20), including variant A, a frameshift mutation in a protein kinase not present in ExAC, with allelic frequency (AF) of 1.27% in MGRB and 17.5% of our cohort (p<0.0001). Multiple common variants (ExAC ≥1%) were more frequent within the cohort compared with population standard. Among these, three functional variants within gene B, encoding a protein involved in modulating immune-responsiveness, (variant B.1, B.2 and B.3, ExAC AF: 1.3%, 0.99% and 2.3%), were found seven times (total) across six individuals (one compound heterozygous B.2/B.3). The exceptional responders cohort was enriched for subjects with higher genetic risk for Disease A, psoriasis and psoriatic arthritis compared with control groups.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Preliminary findings suggest individuals harbouring functional variants in genes promoting immune tolerance may be more responsive to PD-1/PD-L1 inhibitors. This may be due to higher basal immune activation, requiring greater reliance on inhibitory checkpoints to maintain homeostasis. Ordinarily, this would be clinically undetectable, however the addition of a pharmacological CPI may more effectively break immune tolerance in this primed environment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    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: 3
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.16-04 - Outcomes of Patients < 70 or ≥70 Years of Age in PACIFIC (ID 13012)

      16:45 - 18:00  |  Author(s): Rina Hui

      • Abstract
      • Slides

      Background

      In the Phase 3 PACIFIC study of durvalumab versus placebo in patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT), the co-primary endpoint PFS was significantly longer with durvalumab (stratified HR 0.52, 95% CI, 0.42–0.65; P<0.0001). In a prespecified analysis, PFS benefit with durvalumab was observed regardless of a 65-year age cutoff. However, median age at NSCLC diagnosis is 70 (CA Cancer J Clin, 2014). We therefore performed subgroup analyses to explore outcomes using a 70-year age cutoff.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind, all-comers study of patients with WHO PS 0/1 who did not progress following ≥2 cycles of platinum-based cCRT. Patients were stratified by age, sex, and smoking history and randomized (2:1) 1–42 days after cCRT to receive durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Co-primary endpoints were PFS (BICR, RECIST v1.1) and OS (not available). Secondary endpoints included ORR, time to death/distant metastasis (TTDM), and safety. Between-treatment endpoint comparisons were performed for patients <70 and ≥70 years.

      4c3880bb027f159e801041b1021e88e8 Result

      As of Feb 13, 2017, 713 patients were randomized; 78% and 22% were <70 and ≥70 years, respectively. Baseline patient and tumor characteristics were generally well balanced across subgroups. However, patients ≥70 were more likely to be male, have PS 1, and, within the placebo arm, to be Asian. Older patients more commonly received carboplatin-based CT than younger patients. Durvalumab demonstrated PFS benefit compared with placebo, regardless if patients were <70 years (median 16.9 vs 5.6 months, HR=0.53, 95% CI: 0.42–0.67) or ≥70 years (median 12.3 vs 6.1 months, HR=0.62, 95% CI: 0.41–0.95). Durvalumab improved TTDM (<70 years: HR=0.53, 95% CI: 0.39–0.71; ≥70 years: HR=0.66, 95% CI: 0.39–1.13) and ORR (<70 years: 27.6% vs 15.4%; ≥70 years: 31.9% vs 17.6%) regardless of age. Younger patients on durvalumab received treatment longer (median total duration 45.5 vs 36.0 weeks). Regardless of treatment, older patients discontinued more due to AEs (durvalumab: 22.0% vs 13.7%; placebo: 16.1% vs 7.8%) and had more grade 5 AEs (durvalumab: 10.9% vs 2.7%; placebo: 9.1% vs. 4.5%). Among patients receiving durvalumab, older patients experienced more all-cause SAEs (42.6% vs 24.9%) and grade 3/4 AEs (41.6% vs 29.4%) but fewer AESIs (56.4% vs 67.9%) than younger patients.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients achieved clinical benefit with durvalumab regardless of age. Increased AEs/SAEs observed in older patients across treatments may reflect age/cCRT related morbidity.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

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

      16:45 - 18:00  |  Author(s): Rina Hui

      • 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

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.16-06 - Expanded Efficacy and Safety Analysis of PACIFIC Based on a PD-L1 Cutpoint of 25% (ID 12992)

      16:45 - 18:00  |  Author(s): Rina Hui

      • Abstract
      • Slides

      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.

      PD-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.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
    • +

      P3.01-35 - Outcomes in Advanced Non-Small Cell Lung Cancer After Discontinuation of PD-1 Checkpoint Inhibitor Due to Toxicity. A Retrospective Study (ID 13628)

      12:00 - 13:30  |  Author(s): Rina Hui

      • Abstract
      • Slides

      Background

      Programmed cell death ligand (PD-1) checkpoint inhibitors have been shown to improve survival in advanced non-small cell lung cancer. Although immune-related adverse events from single agent anti PD-1 or PDL-1 are manageable, severe toxicities require treatment discontinuation. There are limited data on patient outcomes after treatment discontinuation and the necessary cessation of treatment can cause concern of disease control for the patient and clinician. This retrospective study examined disease outcomes in patients after discontinuation of PD-1 checkpoint inhibitor due to toxicity.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients treated with pembrolizumab or nivolumab monotherapy for advanced non-small cell lung cancer at our cancer centre were identified. A retrospective review of electronic and paper records was performed. Information including patient baseline characteristics, progression- free survival, overall survival, toxicity leading to treatment discontinuation and time to progression after treatment cessation were obtained. Imaging was reviewed to confirm events of disease progression.

      4c3880bb027f159e801041b1021e88e8 Result

      54 advanced non-small cell lung cancer patients treated between 2012 and 2017 with single agent pembrolizumab or nivolumab were included in the analysis. 8 (14.8%) patients experienced toxicity necessitating treatment discontinuation. Baseline characteristics including age, ECOG performance status, prior lines of therapy and smoking status were similar in patients with or without severe immune-related toxicities. Pneumonitis was the most common toxicity requiring treatment cessation (n=4). Other toxicities included colitis (n=1), vasculitis (n=1), myositis (n=1) and bullous pemphigoid (n=1). The overall survival at 1 year was 42.6% for all patients versus 37.5% for patients with toxicities requiring treatment cessation. 2 of the patients with pneumonitis died as a result of this toxicity prior to achieving disease control. The patient with bullous pemphigoid and those survived pneumonitis had not experienced disease progression at time of analysis (all censored, alive and progression free for minimum of 6 months after treatment discontinuation). Time to progression was <5 months in the patients with colitis, myositis and vasculitis.

      8eea62084ca7e541d918e823422bd82e Conclusion

      With the limitations of this small study at a single site, patients requiring treatment cessation from toxicity had comparable progression-free and overall survival to those without severe toxicities. The risk of Grade 5 immune- related pneumonitis might have contributed to the numerically lower survival rates in the group that experienced toxicity. Prolonged disease control was observed in patients who survived pneumonitis despite treatment discontinuation.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    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
    • +

      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): Rina Hui

      • 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.

      a9ded1e5ce5d75814730bb4caaf49419

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.