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federica Grosso



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    P1.06 - Mesothelioma (ID 169)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.06-16 - Molecular Signature in Malignant Pleural Mesothelioma (MPM). Preliminary Data of Rames Study (ID 254)

      09:45 - 18:00  |  Author(s): federica Grosso

      • Abstract

      Background

      MPM is an uncommon cancer with limited therapeutic options and poor clinical outcomes. The relative rarity of these tumor has limited the identification of MPM-driver molecular as well as the development of specific drugs

      Method

      RAMES study evaluated the second-line efficacy of gemcitabine/ramucirumab treatment vs. gemcitabine/placebo.

      From December 2016 to July 2018 (end of enrolment), 164 patients (pts) were admitted to this study.

      We evaluated by NGS the mutational profile of a panel of 34 genes (ACTB, ACTG1, ACTG2, ACTR1A, BAP1,CDH8, CDK4, CDKN2A, CDKN2B, COL3A1, COL5A2, CUL1, DHFR, GOT1, KDR, KIT, MXRA5, NF2, NFRKB, NKX6,-2, NOD2, PCBD2, PDZK1IP1, PIK3CA, PIK3CB, PSMD13, RAPGEF6, RDX, SETDB1, TAOK1, TP53,TXNRD1, UQCRC1, XRCC6).

      We reported the results of the first 87 pts (54%): hystotype was epithelioid in 70 pts (80%), biphasic in 14 pts (16%) and sarcomatoid in 3 pts (4%). Median age was 63 years (range 45-81). 70 pts were male (80%) and 17 pts were female (20%). In the present analysis, we included 55 pts in stage III (63%), 26 pts in stage IV (30%) and 6 pts whose stage was unknown. Median first-line PFS platinum/pemetrexed therapy was for 5.75 months (I.C. 95% 4.75-6.76). PFS was ≤6 months for 40 pts (49%), and 6 months for 41 pts (51%).

      Result

      187 functional somatic mutations were identified. Genomic alterations/patient were 1 gene in 29 pts (33%), 3 genes in 18 pts (21%) and ≥5 genes in 2 pts (2%). The most frequent somatic mutations were RDX in 35 pts (40%), MXRA5 in 20 pts (23%), BAP1 in 13 pts (15%) and ACTG 1 in 9 pts (11%). When patients were collated by stage, the most frequent mutations were: MXRA5 in 16 pts in stage III (29%), BAP1 in 5 pts in stage IV (19%) and RDX in 16 pts in stage IV (62%). The percentage of somatic mutations in patients with PFS as first-line chemotherapy for ≤6 and >6 months was 2.2 and 1.6 (p=0.032), respectively. The most frequent mutations/patient for ≤6 and >6 months PFS were: RDX in 14 pts (35%) with PFS < 6, RDX in 19 pts (46%) with PFS >6 and MXRA5 in 11 pts (27%) with PFS >6.

      Conclusion

      This preliminary data suggests a possible role that a genetic signature may play in distinguishing MPM with different clinical-pathological features. The results are expected to be clarified further in the second step of the study, which is ongoing.

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    P2.06 - Mesothelioma (ID 170)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.06-01 - STELLAR Trial: Radiological Response Patterns of TTFields Plus Chemotherapy in First-Line Treatment of Malignant Pleural Mesothelioma (ID 2533)

      10:15 - 18:15  |  Author(s): federica Grosso

      • Abstract
      • Slides

      Background

      Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable, medical device. TTFields have significantly extended survival of glioblastoma patients. In-vitro, human malignant pleural mesothelioma (MPM) cells were highly susceptible to TTFields. In the STELLAR trial [NCT02397928], patients with unresectable MPM treated with first-line chemotherapy in combination with TTFields had a significantly higher median overall survival compared to historical controls (18.2 Vs. 12.1 months). We analyzed radiological data from STELLAR patients whose tumors responded while receiving the combined therapy.

      Method

      The trial accrued 80 patients with unresectable, previously untreated mesothelioma who were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin (at standard dosing). Inclusion criteria: ECOG PS of 0-1, pathologically proven mesothelioma and at least one measurable lesion according to modified RECIST criteria. Patients were followed q3w (CT scan q6w) until disease progression. Radiological assessments were done at each study site. EOCG status and cancer-related pain were assessed until disease progression using a visual analog scale.

      Result

      Partial responses (PRs) were seen in 40.3% of evaluable patients and clinical benefit (PR+SD) was seen in 97.2% of patients. The median time between treatment start and PR was 1.8 (1.4-4.4) months). All patients presenting with PR during the STELLAR study had continuous reduction in the total sum of lesion diameters, suggesting no initial/pseudo-progression. 83% of the patients who responded to the combined therapy finally had disease progression within median response duration of 5.7 (1.4-13) months, per Kaplan-Meier Estimator. One patient did not progress for more than 27 months. Median time to deterioration in performance status was 13.1 months. Average pain score was lower compared to baseline during the first 7 months of treatment and higher later with a median time to a clinical significant 33% increase in pain of 8.4 months. Compliance with TTFields was 68% (16.3 hours/day) during the first 3 months of therapy. No TTFields-related other than expected dermatitis below the arrays were reported.

      Conclusion

      The STELLAR study showed significant survival extension in previously untreated MPM patients. Response rates were similar to that of current SOC treatment, but lasted longer with the addition of TTFields. TTFields was not associated with a decrease in performance status or an increase in pain. TTFields in combination with chemotherapy are efficacious in MPM vs chemotherapy alone reported in historical data.

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