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Conrad Lewanski



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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: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-70 - Efficacy and Safety of Second- or Third-Line Nab-Paclitaxel + Durvalumab in Patients with Advanced NSCLC (ABOUND.2L+) (ID 13042)

      16:45 - 18:00  |  Author(s): Conrad Lewanski

      • Abstract

      Background

      Cytotoxic chemotherapy may enhance the effect of immune checkpoint blockers (ICBs) through interaction with the immune system (immunostimulation) and cancer cells (increased antigenicity). The phase II ABOUND.2L+ trial investigated second-/third-line nab-paclitaxel monotherapy, nab-paclitaxel + CC-486, or nab-paclitaxel + durvalumab in patients with previously treated advanced-stage NSCLC. This report presents an updated analysis of the efficacy and safety from the nab-paclitaxel + durvalumab treatment arm.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients ≥ 18 years with advanced NSCLC and no more than 1 prior line of platinum-containing chemotherapy (ICBs in prior line, first/second, allowed) were included. Patients were treated with nab-paclitaxel on days 1 and 8 + durvalumab 1125 mg on day 15 of a 21-day cycle until unacceptable toxicity or progressive disease as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or immune-related RECIST v1.1. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 79 patients were assigned to nab-paclitaxel + durvalumab. The median age of patients in that arm was 63.0 years; 68.4% were male, 97.5% were white, 77.2% had ECOG performance status 1, and 69.6% had nonsquamous histology; 8 patients received prior ICBs. Median and 1-year PFS were 4.5 months (95% CI: 3.45-5.88) and 25.7% (95% CI 16.3-36.2); median PFS in those with and without prior ICB treatment was NE (95% CI 1.38-NE) and 4.4 months (95% CI 2.96-5.68) and in those with squamous and nonsquamous histology was 6.0 months (95% CI 2.99-7.75) and 4.2 months (95% CI 2.86-5.75). The ORR was 27.8%, and DCR was 70.9%. Median OS was 10.1 months (95% CI: 7.75-NE). Median percentage of per protocol dose was 87.5% for nab-paclitaxel and 82.9% for durvalumab. All patients had at least 1 treatment-emergent adverse event (TEAE), and 67.9% had at least 1 grade 3 or 4 TEAE. Common TEAEs of special interest (all grades) included peripheral neuropathy (grouped term; 37.2%), diarrhea (34.6%), anemia (30.8%), dyspnea (25.6%), nausea (24.4%), cough (24.4%), pyrexia (19.2%), and neutropenia (17.9%). TEAEs leading to dose interruption/reduction (nab-paclitaxel and/or durvalumab) were reported in 73.1% of patients, and those leading to discontinuation in 11.5%.

      8eea62084ca7e541d918e823422bd82e Conclusion

      nab-Paclitaxel + durvalumab demonstrated promising antitumor activity and manageable toxicity in second- or third-line treatment of patients with advanced NSCLC. NCT02250326.

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      P1.01-93 - Quality of Life in Patients with Advanced NSCLC Treated in Second- or Third-Line with Nab-Paclitaxel + Durvalumab: ABOUND.2L+ (ID 12993)

      16:45 - 18:00  |  Author(s): Conrad Lewanski

      • Abstract

      Background

      Quality of life (QoL) can be adversely affected in patients with advanced NSCLC, particularly those receiving second- or third-line treatment. In these patients, checkpoint inhibitors are a recommended treatment option. Through multiple mechanisms, including the release of tumor antigens via tumor cell lysis, chemotherapy can augment immunotherapeutic effects, which is the rationale for combining chemotherapy with immunotherapy agents. The phase II ABOUND.2L+ trial investigated second- or third-line nab-paclitaxel either alone or in combination with CC-486 or durvalumab in patients with advanced NSCLC. The objective of this analysis is to report QoL outcomes in patients treated with nab-paclitaxel + durvalumab from the ABOUND.2L+ trial.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Enrolled patients were ≥ 18 years with advanced NSCLC and no more than 1 prior line of platinum-containing chemotherapy. Immunotherapy in a prior line, first or second, was allowed. Patients were treated with nab-paclitaxel on days 1 and 8 + durvalumab 1125 mg on day 15 of a 21-day cycle. Treatment continued until unacceptable toxicity or disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or immune-related RECIST v1.1. The primary endpoint was progression-free survival. QoL was a prespecified exploratory endpoint assessed using the Lung Cancer Symptom Scale (LCSS), EuroQol 5D-5L, and EORTC QLQ-C30 on day 1 of each cycle, and was examined through 6 cycles of treatment for this analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 79 patients were assigned to the nab-paclitaxel + durvalumab arm. The median age was 63.0 years. Most patients were white (97.5%), male (68.4%), and had ECOG PS of 1 (77.2%). For the entire study, baseline and ≥ 1 postbaseline QoL assessments were completed by 58 (73.4%) patients. 41 patients completed 6 cycles of treatment with nab-paclitaxel + durvalumab. After cycle 6, the mean change from baseline in LCSS total score and pulmonary symptom score was 0.1 and −0.2, respectively. LCSS hemoptysis score improved relative to baseline at every treatment cycle; mean change from baseline after 6 cycles was 0.8. Mean change from baseline in the EuroQol 5D-5L visual analog scale score and EORTC QLQ-C30 global health status/QoL scale score after 6 cycles of treatment was 2.5 and −1.19, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In general, patients with advanced NSCLC treated with second- or third-line nab-paclitaxel + durvalumab maintained their QoL through 6 cycles of treatment. NCT02250326.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • 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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      P1.13-17 - Multicentre Phase II Trial of First-Line Afatinib in Patients with Suspected/Confirmed EGFR Mutant NSCLC: ctDNA & Long-Term Efficacy (ID 11908)

      16:45 - 18:00  |  Author(s): Conrad Lewanski

      • Abstract
      • Slides

      Background

      Efficacy of afatinib in EGFR mutant patients with comorbidities or those with suspected EGFR mutations unfit for chemotherapy is poorly explored. We evaluated afatinib in this population, with serial plasma ctDNA to investigate the role of molecular EGFR genotyping and monitoring.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Phase-II trial enrolled NSCLC patients with comorbidities precluding chemotherapy, and either (i) EGFR-mutation, PS 0-3, or (ii) suspected EGFR-mutation (tissue unavailable/failed genotyping), never/former-light smoker, adenocarcinoma, and PS 0-2. Afatinib (40mg daily) given until progression/toxicity. Blood samples obtained at baseline and 12-weekly until discontinuation; plasma ctDNA performed using InVisionSeq™ (amplicon-based NGS).

      4c3880bb027f159e801041b1021e88e8 Result

      39 patients recruited (14 UK centres). Median age 72 years; 27 PS 0-1/12 PS 2-3. 21 patients (54%) had known tissue EGFR-mutations. Additional 8 patients with unknown tissue status (8/17;47%), were ctDNA EGFR-mutant, making 74% EGFR-mutant in total (29/39). Combined tissue and ctDNA data identified 21 patients with common mutations (exon 19/L858R), 8 with rare mutations (exon 18/20), and 10 suspected only. Corresponding median PFS of these cohorts were 10.2/3.9/5.3 months, with 6-month PFS of 71/38/50% all exceeding the 30% target; median OS were 24.8/5.7/11.4 months (p<0.001). Therefore, all patient groups benefitted; known EGFR-mutants having best outcomes. In April 2018, 5/39 patients survived >36 months, including 4/39 progression-free (median follow-up 33 months, maximum 55). Patients with ctDNA mutation clearance during afatinib treatment had substantially improved outcomes compared to those without clearance (Figure). 40% (4/10) of mutant cases who discontinued after 3 cycles because of progressive disease developed an exon 20 EGFR-mutation.

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      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients unsuitable for chemotherapy with confirmed/suspected EGFR-mutations by tissue or ctDNA benefit from afatinib. Serial ctDNA is a potentially useful stratification and monitoring tool; amplicon-based ctDNA analysis can identify EGFR mutations when tissue is unavailable. Exon 20 mutations were observed at acquired resistance. ctDNA clearance during afatinib treatment is strongly associated with better PFS/OS.

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