ESMO Supporter 2018

Displaying One Session

Hall B3 - Room 21 Proffered Paper session
Date
19.10.2018
Time
14:00 - 15:30
Location
Hall B3 - Room 21
Chairs
  • Rick L. Haas (Amsterdam, NL)
Proffered paper session - Sarcoma Proffered Paper session

1601O - Natural history of sarcomas and impact of reference centers in the nationwide NETSARC study on 35,784 patients (pts) from 2010 to 2017.

Presentation Number
1601O
Lecture Time
14:00 - 14:12
Speakers
  • Jean-Yves Blay (Lyon, FR)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30

Abstract

Background

We report on the characteristics and determinants of outcome of the 35784 pts included in the nationwide NETSARC/RREPS study since its inception.

Methods

NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTB), funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients. Patients’ characteristics and follow-up are collected in a database regularly monitored. Descriptive, uni and multivariate analysis of prognostic factors were conducted in the incident (n = 29497) pts population as well as on pts diagnosed before 1/1/2010 (n = 6287), presented to an MDTB after 1/1/10.

Results

We first investigated predisposing and associated conditions: among the 35784, previous cancer, previous RT, NF1, Li-Fraumeni, were reported in 12.5%, 3.6%, 0.7%, 0.1% of pts respectively. 71 of the 35784 (0.2%) pts had 2 or 3 different diagnosis of sarcomas: 28%, 7%, 6%, 3% of these pts had an history of previous cancer, NF1, Li-Fraumeni, Ollier disease (p < 0.001). Prognostic factors of pts outcome at initial diagnosis were then analyzed: male gender, age, size, depth, grade 3, NF1, previous RT were all associated with a worse overall (OS) and progression free survival (PFS) in the incident pts population in univariate and multivariate analysis, while GIST, intermediate malignancy histologies, and surgery in a Netsarc center (HR:0,63) were positively correlated with OS and PFS (p < 0.001 for all). Similar results were obtained in the 6287 pts diagnosed before 2010 for OS. In pts in advanced phase, survival was superior to that reported in the literature with a median of 27 months for all sarcomas but GIST. Median OS was not reached for GIST and tumor of intermediate malignancy (58% and 76% at 5 years respectively). NF1, previous RT, and treatment outside a reference center were again associated with a worse OS in multivariate analysis.

Conclusions

In this nationwide registry of sarcoma patients, unreported prognostic characteristics sarcoma pts were identified.Treatment in a reference center reduces the risk of relapse and death.

Legal entity responsible for the study

NETSARC and French Sarcoma Group.

Funding

French NCI ( INCA).

Disclosure

J-Y. Blay: Research support and honoraria: Roche, Novartis, Bayer, GSK, Lilly, MSD, BMS, Ignyta, Deciphera, PharmaMar. All other authors have declared no conflicts of interest.

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Proffered paper session - Sarcoma Proffered Paper session

1602O - Outcome following unplanned excision in soft tissue sarcoma. Results of a multicentre study including 728 patients.

Presentation Number
1602O
Lecture Time
14:12 - 14:24
Speakers
  • Maria A. Smolle (Graz, AT)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30

Abstract

Background

Misdiagnosis of soft tissue sarcoma (STS) is common, due to their rarity and unclear clinical presentation. As a result, unplanned excisions (UE) may occur, most often necessitating further treatment at specialised tumour centres. Therapy includes re-resection and adjuvant radiotherapy (ARTX), being associated with increased morbidity. Results on UE’s impact on overall survival (OS) are contradictory, though.

Methods

728 STS patients (376 male, 352 female; mean age: 58 years) undergoing primary surgery or re-resection following UE at three tumour centres were retrospectively included. Median follow-up was 5.5 years. Differences between UE- and non-UE-patients were analysed using chi-square and t-tests. Log-rank and Gray’s tests were applied for time-to-event analyses. Based on differences between UE- and non-UE-patients at baseline, a propensity score of being in the UE-group was estimated. Based on the propensity score, an inverse-probability-of-UE-weight (IPUEW) was calculated. This allowed re-calculation of time-to-event analyses following adjustment for imbalances between non-UE- and UE-patients.

Results

UE had been performed in 281 patients (38.6%), with similar incidences at the three tumour centres. Small (p < 0.005) and superficially located STS (p < 0.005) with a long history of symptoms (p < 0.005), male gender (p = 0.05) and young age (p = 0.036) raised the risk of an UE being performed. At re-resection, plastic reconstruction (p < 0.005) and ARTX (p = 0.041) were significantly more common in UE-patients. In the univariate analysis, UE-patients had a significantly better OS (5-/10-year OS: 78.6%/63.3% for UE; 70.6%/57.9% for non-UE; p = 0.028). Due to a strong correlation between positive prognostic factors and a prior UE, survival analyses were re-calculated after weighting for the IPUEW. As a result, the prognostic benefit of UE in terms of OS was lost (p = 0.241).

Conclusions

Morbidity is raised in patients following UE due to increased necessity of plastic reconstruction and ARTX. However, there is no direct impact of UE on OS. Nevertheless, it is arguable whether a more aggressive approach in the UE-group compensates for the inappropriate primary resection. Thus, UE must be avoided by all means.

Legal entity responsible for the study

Medical University of Graz.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Proffered paper session - Sarcoma Proffered Paper session

LBA66 - A phase II/III trial of hafnium oxide nanoparticles activated by radiotherapy in the treatment of locally advance soft tissue sarcoma of the extremity and trunk wall

Presentation Number
LBA66
Lecture Time
14:24 - 14:36
Speakers
  • Sylvie Bonvalot (Paris, FR)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30

Abstract

Background

NBTXR3 is a first-in-class Hafnium-Oxide nanoparticle intratumorally (IT) injected. When activated by radiotherapy (RT), it allows for a higher energy deposit than RT alone, yielding an increased tumoral cell death.

A phase I study in soft tissue sarcoma (STS) showed that a single NBTXR3 IT injection at 10% of the baseline tumor volume with preoperative RT was technically feasible with manageable toxicity and clinical activity was observed.

Methods

In this international, multicenter, randomized, open-label phase II/III study, patients (pts) with locally advanced STS of the extremity and trunk wall received either a single IT injection of NBTXR3 followed by RT or RT alone (1:1 ratio), both followed by surgical resection. RT was by Intensity Modulated RT or 3D-RT of 2Gy/25 fractions (total 50 Gy). The primary endpoint was the pathological Complete Response Rate (pCRR) defined as the percentage of pts presenting ≤5% of residual viable cancer cells (EORTC guidelines) evaluated by a blind Central Review Board. Key secondary endpoints included negative surgical margins (R0) and safety.

Results

In the intent-to-treat full analysis set population (n=179), which included all pts who were randomized and stratified by STS histological subtype, the pCRR was 16.1% vs 7.9 (p=0.0448) and the R0 rate was 77.0% vs 64.0% (p=0.0424) for NBTXR3+RT and RT alone respectively. NBTXR3 caused injection-site pain in 12 (13.5%) pts. It was also associated with grade 3-4 acute immune reactions in 7 (7.9%) pts, but these adverse events were of short duration, manageable, and resolved spontaneously in some cases. Outside the injection, NBTXR3 was very well tolerated and its safety profile was comparable to RT alone.

Conclusions

NBTXR3 activated by RT was signicantly superior to RT alone and this trial met both primary and secondary endpoint with a positive safety profile. NBTXR3 represents a new option for preoperative treatment for locally advanced STS.

These data support ongoing studies investigating NBTXR3 in recurrent/metastatic HNSCC or metastatic non-small cell lung cancer [NCT03589339]; HNSCC [NCT01946867; NCT02901483]; prostate [NCT02805894], liver [NCT02721056] and rectal cancers [NCT02465593].

Clinical trial identification

NCT02379845

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Proffered paper session - Sarcoma Proffered Paper session

Invited Discussant 1601O, 1602O and LBA66

Lecture Time
14:36 - 14:51
Speakers
  • Rick L. Haas (Amsterdam, NL)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30
Proffered paper session - Sarcoma Proffered Paper session

1603O - Initial Results of Phase 1 Study of DCC-2618, a Broad-spectrum KIT and PDGFRa Inhibitor, in Patients (pts) with Gastrointestinal Stromal Tumor (GIST) by Number of Prior Regimens.

Presentation Number
1603O
Lecture Time
14:51 - 15:03
Speakers
  • Suzanne George (Boston, US)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30

Abstract

Background

DCC-2618, a kinase switch control inhibitor, broadly inhibits mutations in KIT exons 9, 11, 13, 14, 17 and 18. Based on clinical activity observed in heavily pretreated GIST pts in a Phase 1 study, DCC-2618 is being evaluated in a Phase 3 study, INVICTUS (NCT03353753), in ≥ 4th line pts. Given the breadth of inhibition of KIT mutations and favorable tolerability profile, the Phase 1 study included expansion cohorts to assess clinical benefit in 2nd and 3rd line GIST pts in advance of the expected initiation of a second Phase 3 study in 2nd line GIST pts by the end of 2018.

Methods

The Phase 1 study includes a dose-escalation component testing oral DCC-2618 dosed QD or BID in 28 day cycles and an expansion phase using the RP2D of 150 mg QDin 6 cohorts, including cohorts for GIST pts based on prior regimens (2nd/3rd, 4th/>4th). RECIST response assements based on local assessment of CT scans were performed every 2 cycles.

Results

At the cut off of April 18, 150 GIST pts were enrolled at dose levels of ≥ 100 mg/d with KIT (141 pts) or PDGFRa- (8 pts) -driven GIST. One pt had SDH-deficient GIST. 114 GIST pts were treated at the 150 mg QD dose, including 19, 27, and 68 pts who previously received 1, 2 or ≥ 3 prior lines of therapy, respectively. For the 114 GIST pts, ORR was 14%, 3-month DCR was 70%, mPFS was 24 weeks with 56% of the pts censored. For the 46 evaluable pts in 2nd/3rd line, ORR was 22%, 3-month DCR was 81% and mPFS was 36 weeks with 61% of the pts censored. Updated ORR, DCR and mPFS will be presented. Grade 3/4 adverse effects (regardless of attribution, in > 1 pt) for all 114 pts treated at 150 mg QD included asymptomatic lipase increase 11, anemia 4, hypertension 3, blood bilirubin increased 3, diarrhea 2, abdominal pain 2, back pain 2, hypophosphatemia 2, hyponatremia 2, hyperkalemia 2.

Conclusions

DCC-2618 demonstrated encouraging clinical benefit and a favorable tolerability profile in GIST pts treated in the 2nd line or later. Clinical benefit as measured by ORR, DCR and mPFS was greater in 2nd/3rd line pts compared to more heavily pretreated pts. Preliminary data from the Phase 1 expansion supports further testing in the planned Phase 3 study in 2nd line GIST.

Clinical trial identification

NCT02571036.

Legal entity responsible for the study

Deciphera Pharmaceuticals, Inc.

Funding

Deciphera Pharmaceuticals, Inc.

Disclosure

S. George, M. Heinrich, P. Chi, M. von Mehren, M. Gordon, N. Somaiah, F. Janku: Research sponsored: Deciphera Pharmaceuticals, Inc.; Scientific advisory board: Deciphera Pharmaceuticals, Inc. A. Razak, K.N. Ganjoo, J. Wolf, J. Rodon Ahnert: Research sponsored: Deciphera Pharmaceuticals, Inc. J.C. Trent: Scientific advisory board: Deciphera Pharmaceuticals, Inc. R. Ruiz-Soto, O. Rosen: Employee: Deciphera Pharmaceuticals, Inc.

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Proffered paper session - Sarcoma Proffered Paper session

LBA67 - Cabozantinib in Patients With Advanced Osteosarcomas and Ewing sarcomas: a French Sarcoma Group (FSG)/ US National Cancer Institute phase II collaborative study.

Presentation Number
LBA67
Lecture Time
15:03 - 15:15
Speakers
  • Antoine Italiano (Bordeaux, FR)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30

Abstract

Background

The prognosis of relapsed and unresectable high-grade osteosarcoma (OS) and Ewing sarcoma (ES) is dismal and unchanged over the last decades. There are no approved drugs in this setting. Pharmacologic inhibition of Met signaling and of aberrant angiogenesis has shown promising results in in several preclinical models of OS and ES.

Methods

These are 2 multicentre single-arm 2-stage phase 2 trials assessing efficacy and safety of cabozantinib in patients (pts) with advanced OS or ES. Pts receive cabozantinib (oral route, adults: 60 mg, children: 40 mg/m²), daily until progressive disease (PD) or unacceptable toxicity. For OS, the primary endpoint is a dual one based on 6-month objective response (OR) and non-progression. Assuming 25% 6-month non-PD (H0), 50% acceptable 6-month non-PD (H1); 5% OR (H0), 20% OR (H1); 5% type I error, 90% power, 41 assessable pts are necessary. The study will be considered as positive if at least 5 patients have OR or 16 patients are progression-free at 6 months. For ES, the primary endpoint is OR. Assuming 5% OR (H0), 20% OR (H1); 5% type I error, 90% power, 41 assessable pts are necessary. The study will be considered as positive if at least 5 patients have OR. Accrual started in 03/2015 in 15 centers of the FSG.

Results

90 pts (45 OS and 45 ES) were included. At the time of statistical analysis, 42 pts with OS and 33 pts with ES were eligible and evaluable for the 1st endpoint after central histological and radiological review. Median age was 34.5 (13–74) and 33 y (13–60) in the OS and ES cohorts respectively. The median number of previous lines of was 3 (1-7) and 4 (1-7) in the OS and ES cohorts respectively. 72 pts (96.0%) had at least one adverse event. 19 OS pts (45.2%) had tumor shrinkage: 5 (11.9%) with partial response (PR) and 14 (33.3%) with stable disease (SD). 19 ES pts (57.6%) had tumor shrinkage: 9 (27.7%) with PR and 10 (30.3%) with SD. 14 OS pts (33.3%) and 8 ES pts (24.2%) were progression-free at 6 months.

Conclusions

Cabozantinib has shown meaningful clinical activity in OS and ES patients with heavily pre-treated advanced disease and reached the primary endpoint of efficacy in both OS and ES cohorts Final efficacy and safety data will be presented at the meeting.

Clinical trial identification

NCT02243605

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Proffered paper session - Sarcoma Proffered Paper session

Invited Discussant 1603O and LBA67

Lecture Time
15:15 - 15:30
Speakers
  • Daniela Katz (Be'er Ya'akov, IL)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30