Virtual Library

Start Your Search

Denis Moro-Sibilot



Author of

  • +

    MA04 - Novel Approaches with IO (ID 900)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
    • +

      MA04.03 - Immunotherapy for Non-Small Cell Lung Cancers (NSCLC) with Oncogenic Driver Mutations: New Results from the Global IMMUNOTARGET Registry (ID 13187)

      13:40 - 13:45  |  Author(s): Denis Moro-Sibilot

      • Abstract
      • Presentation
      • Slides

      Background

      Prospective data on immunotherapy for NSCLC with oncogenic driver mutations are limited. We recently reported first results from the global IMMUNOTARGET registry (Mazières, ASCO 2018). Here, we present new data for PD-L1 and mutation subgroups.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In 2017, we started an international retrospective registry study ("IMMUNOTARGET") for patients with advanced NSCLC, known driver mutations (KRAS, EGFR, ALK, ROS1, BRAF, HER2, MET and RET) and PD-L1 immune checkpoint inhibitor therapy. The registry is approved by University of Toulouse and Swissethics, and funded by University of Toulouse and Cantonal Hospital of Lucerne. Anonymized real-world data submitted to the coordinating center include: patient and tumor characteristics, mutation test methods and results, systemic therapy lines, immune related adverse events, best response by RECIST, survival, and tumor PD-L1 expression (optional). Statistical calculations including best response, median PFS and OS are done at University of Toulouse.

      4c3880bb027f159e801041b1021e88e8 Result

      In April 2018, the registry included 551 pts from Europe, USA, Israel and Australia. Patients were 50% male/female, 28% current smokers, median age 60 years (range 28-83), 85% had PS0/1. Most (73%) tumors were stage IV at diagnosis, almost all (96%) were adenocarcinomas. Molecular classification by dominant driver mutation: KRAS=271 (49%), EGFR=125 (23%), BRAF=43 (8%), MET=36 (7%), HER2=29 (5%), ALK=23 (4%), RET=16 (3%), ROS1=7 (1%), 1 (0.2%) not classified (ALK+RET+MET). Most pts received nivolumab (466) or pembrolizumab (48) and were treated with immunotherapy in second or third line (67%). The median number of cycles was 5 (range 1-68). Fifty (11%) pts had grade 3-5 toxicity. Median OS from start of immunotherapy was 13.3 months, median PFS was 2.8 months. Best response was PR/CR in: KRAS=26%, BRAF=24%, ROS1=17%, MET=16%, EGFR=12%, HER2=7%, RET=6%, ALK=0%. Percentage of PD-L1 positive cells was available for 177 pts: 0%=71 (40%), 1-49%=46 (26%), 50-100%=60 (34%). Median % of positive cells was highest for ROS1 (90%), BRAF (50%), MET (30%) and RET (26%) mutant tumors. PD-L1 positivity was predictive for improved PFS in KRAS and EGFR mutant tumors. PD-L1 status was known in 18 tumors with ALK, ROS1 or RET rearrangements: 5 had 0%, 4 had 1-49% and 9 had 50%-100%. No tumor remissions were observed in this subgroup. The registry remains open, updated results will be presented at the conference.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although response rates were lower than in KRAS mutant NSCLC, individual tumors with other driver mutations responded to immunotherapy. PD-L1 expression may not accurately predict clinical benefit from immunotherapy in some molecular subgroups, better markers are needed.

      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.

  • +

    MA14 - Survivorship, Socioeconomic and End-of-Life Considerations (ID 915)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 205 BD
    • +

      MA14.02 - Use and Impact of A Systematic Advanced Care Planning in Hospitalized Lung Cancer Patients: A Prospective Study. (ID 13997)

      10:35 - 10:40  |  Author(s): Denis Moro-Sibilot

      • Abstract
      • Presentation
      • Slides

      Background

      End-of-life communication is crucial, particularly for cancer patients. In usual practice, advanced care planning discussions with the patients are uncommon and rarely documented. The aim of this study was to investigate the impact of advanced care planning on intensity of care in cases of organ failure in lung cancer patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This prospective study was performed at the Grenoble University Hospital in France. Consecutive patients hospitalized in thoracic oncology unit between 01/28/2014 and 03/31/2016 were included and followed up to 12/31/2016. At each hospital admission, lung cancer patients benefited from advanced care planning. We defined 3 intensities of care: intensive care, maximal medical care and exclusive palliative care. The propositions of care could be modified during the hospitalization. Patients’ wishes should be received.

      4c3880bb027f159e801041b1021e88e8 Result

      Data of 715 hospitalizations corresponding to 473 patients were studied. Hundred fifty nine patients had a second hospitalization and 69 a third. At first admission, 247 (52%) patients had a performance status of 0 to 2, 186 (39%) were not yet treated for the cancer and 165 (35%) in progression. Main reasons of admission were an acute disease (n=208, 44%) and supportive care of cancer symptoms (n=167, 35%).

      During the three first admissions, 173 (25%) patients developed an organ failure. Among them, 56 (32%) had intensive care proposition, 104 (61%) maximal medical care, and 13 (7%) exclusive palliative care. Median time between admission and organ failure was 9 days [IQR 25%-75%, 3-13]. All patients benefited from intensity of care equal or lower than the proposed intensity of care. Among patients planed for intensive care, 17 (30%) patients received intensive care, 22 (39%) maximal medical care and 17 (30%) exclusive palliative care. Thirteen of the 39 patients not admitted in ICU despite organ failure and previous proposition of intensive care were considered too well by the oncologist. Patients’ wishes were recorded for 158 (91%) patients, and a discussion about end of life conditions was led with 116 (73%) patients or families.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In case of organ failure, an advanced care planning appears helpful to provide reasonable intensity of care. The proposition of care seems to be adapted to the patient’s general condition and cancer characteristics. 3/4 of the patients with an organ failure benefited from a discussion about end of life conditions.

      ClinicalTrials.gov Identifier: NCT02852629

      Funding from the publicly funded nonprofit organization Cancéropole Lyon Auvergne Rhône-Alpes (CLARA).

      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.

  • +

    OA12 - Novel Therapies in MET, RET and BRAF (ID 921)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 106
    • +

      OA12.03 - Activity of Crizotinib in MET or ROS1 Positive (+) NSCLC: Results of the AcSé Trial. (ID 12937)

      15:35 - 15:45  |  Presenting Author(s): Denis Moro-Sibilot

      • Abstract
      • Presentation
      • Slides

      Background

      Crizotinib was registered for ALK+ NSCLC in 2013 and recently for ROS1+ stage IV NSCLC. To generate high evidenced-based knowledge and to prevent off-label use, the French National Cancer Institute (INCa) launched the AcSé Program: equal access to tumor molecular diagnosis including an exploratory phase II trial. AcSé allows nationwide safe and controlled access to crizotinib off-label.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Biomarkers were identified with INCa molecular genetic platforms. Patients with amplification [amp] MET or mutation [mut] MET or translocation [tlc] ROS1 advanced NSCLC and not eligible for any other trial, were proposed crizotinib 250 mg BID. Tumor response was evaluated every 2 months (mo) using RECIST v1.1. The primary endpoint was the objective response rate (ORR) at 2 mo (complete + partiale response). A two-stage Simon design was applied to each cohort. Median and 95% confidence interval (CI) was estimated through Kaplan-Meier for progression-free survival (PFS), overall survival (OS), and response duration. Response duration was the delay between CR/PR and first progression/death or last follow-up.

      4c3880bb027f159e801041b1021e88e8 Result

      From 08/2013 to 03/2018, 5407 patients from 186 centers entered the biomarker program. Tumor alterations found in patients were: ROS1 tlc in 77/4050; MET amp (≥6 copies/diploid genome) in 251/4171; MET mut in 76/1007.

      Overall, 90 patients (median age, 63 years [30–92]) received crizotinib 250 mg BID.

      #12937.jpg

      73 grade ≥3 adverse events (AEs) or SAE were reported in 70/90 patients. Grade ≥3 AEs were: hematologic toxicities (23%) including neutropenia (11%), and general disorders (16%) including fatigue (10%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study confirms the excellent response rate of crizotinib in the ROS1+ population. Response rate in the MET mut population is comparable to the MET amp population. In addition, the response rate to crizotinib in the MET mut population is lower than that in the PROFILE 1001 study. The tolerance profile is good as previously reported.

      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.

    • +

      OA12.05 - Vemurafenib in Patients Harboring V600 and Non V600 BRAF Mutations: Final Results of the NSCLC Cohort from the AcSé Trial. (ID 12936)

      16:00 - 16:10  |  Author(s): Denis Moro-Sibilot

      • Abstract
      • Presentation
      • Slides

      Background

      BRAF mutations are found in 2-3% of NSCLC. BRAF inhibitors reportedly have antitumor activity. The French National Cancer Institute (INCa) launched a program giving nationwide access to vemurafenib for cancer patients with BRAF-mutated tumors and supported molecular screening. We herein report the NSCLC cohort results.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      BRAF mutational status was assessed on INCa molecular genetic centers by direct sequencing or NGS. Patients with mutated BRAF (V600E and others mutations) progressing after ≥1 standard treatment were proposed vemurafenib 960 mg BID. Objective Response Rate (ORR) was assessed using RECIST v1.1 every 8 weeks. A sequential Bayesian approach was planned to allow early stopping using an inefficacy bound for ORR of 10%. If no early stopping occurred, the treatment was considered worthy for further evaluation if there was a 90% probability that the estimated ORR is ≥30%, the efficacy bound.

      4c3880bb027f159e801041b1021e88e8 Result

      From 10/2014 to 10/2017, 118 NSCLC patients were enrolled: 101 with BRAF V600E and 17 with other potentially activating mutations (4 G466, 4 G469, 1 G596, 5 K601, and 3 N581). Median age was 68 years (range 34–85), 71% smokers, 48% females, 100% non-squamous histology, and 20% with ECOG PS 2. Most frequent grade ≥3 adverse events (AEs) were asthenia (9% of patients), epidermoid carcinoma (6%), dermatitis (5%), and increased GGT (5%). Three toxic deaths were reported: 1 nausea and vomiting leading to dehydration, 1 pneumonia, and 1 neutropenic sepsis.

      #12936.jpg

      Nine patients were still on treatment at the cut-off date, 106 had stopped vemurafenib (65 PD, 26 AEs, 3 deaths, 1 doctor’s decision, 11 patient’s decisions).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Vemurafenib provided reasonable response rate and extended PFS in pretreated NSCLC patients with BRAF V600E mutations but was not effective in those with other BRAF mutations. These results emphasize the need of integrating BRAF V600E in routine biomarkers screening.

      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
    • +

      P1.01-66 - Randomized Phase II Evaluating EGFR-TKI Associated with Anti-Estrogen in Women with Non-Squamous Advanced Stage NSCLC: IFCT-1003 LADIE Trial. (ID 13740)

      16:45 - 18:00  |  Author(s): Denis Moro-Sibilot

      • Abstract

      Background

      The incidence of lung cancer is increasing dramatically in women with recent findings as the preferential involvement of the EGFR pathway and the potential impact of hormonal factors in women. Preclinical data have shown that the combination of an EGFR-TKI with an anti-estrogen could overcome resistance to EGFR-TKI.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      IFCT-1003 LADIE Trial was a 2x2 arms parallel open-label randomized phase II trial. PS 0-2 post-menopausal women with advanced stage lung adenocarcinoma were treated with gefitinib (G 250 mg/day) vs. G + fulvestrant 500 mg / month with a supplementary dose at day 15 (G+F) in the EGFR mutated group (EGFR+) in 1st or 2nd line setting or with erlotinib (E 150 mg/day) vs. E + fulvestrant (E+F) in the EGFR wild-type group (EGFR WT) in 2nd or 3rd line setting until progression or unacceptable toxicity. Primary objective was progression-free survival (PFS) at 3 and 9 months for EGFR WT and EGFR+ patients, respectively.

      4c3880bb027f159e801041b1021e88e8 Result

      From 02/2012 to 03/2017, 204 pts (G 104, G+F 100) and 175 (E 87, E+F 88) were enrolled in the EGFR+ and EGFR WT cohorts respectively. The median number of fulvestrant injections was 10 in the G+F group and 3 in the E+F group. The tolerance was correct (grade 3/4: 24.2% in the G+F group vs 21.3% in the G group, 16.0% in the E+F group vs 13.8% in the E group) and no treatment-related death. In the EGFR+ cohort, the primary endpoint was reached as 54 pts in the G+F group were non-progressive at 9 months. Nevertheless, addition of F to G was not associated with significant better PFS (9.9 vs 10.1 months) or OS (22.1 vs 29.9 months). In the EGFR WT cohort, the primary endpoint was not reached as 29 patients were non-progressive at 3 months. Here also, addition of F to E was not associated with better outcome (PFS 1.8 vs 2.0 and OS 10.0 vs 7.3 months). No PFS difference was observed in the subgroup of patients with positive staining for REα.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Addition of fulvestrant to EGFR-TKI is feasible and is associated with good PFS in the EGFR mutated group. Nevertheless, the lack of benefit associated with the combination of fulvestrant to EGFR-TKI does not support its future development in a phase 3 trial in women with NSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53