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Jan P Van Meerbeeck
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MA12 - Mesothelioma Surgery and Novel Targets for Prognosis and Therapy (ID 913)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 202 BD
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MA12.06 - STELLAR – Final Results of a Phase 2 Trial of TTFields with Chemotherapy for First-Line Treatment of Malignant Pleural Mesothelioma (ID 13806)
11:05 - 11:10 | Author(s): Jan P Van Meerbeeck
- Abstract
- Presentation
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. In-vitro, human mesothelioma cells were highly susceptible to TTFields. TTFields have been shown to significantly extend survival of patients with glioblastoma when added to chemotherapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
The trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin (at standard dosing). Inclusion criteria included 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. The primary endpoint was overall survival (OS) and secondary endpoints were response rate, progression free survival (PFS) and toxicity. This prospective, single arm study assumed an historical control with a median survival of 12.1 months (Vogelzang et al. 2003). The sample size provides 80% power with a two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months.
4c3880bb027f159e801041b1021e88e8 Result
All 80 patients were enrolled between 2016 and 2017, with a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 56% smokers. 16% (13 patients) had metastatic disease and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology. Compliance with TTFields was 68% (16.3 hours/day) during the first 3 months of therapy and 63% (50 patients) received carboplatin.
Median OS was 18.2 months (95% CI 12.1-25.8) compared to 12.1 months in the historical control. Median PFS was 7.6 months (95% CI 6.7-8.6) compared to 5.7 months in the historical control. Partial responses were seen in 40.3% of patients and clinical benefit (PR+SD) was seen in 97.2% of patients. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Only 4 patients (5%) had grade 3 dermatitis. The following grade 3-4 systemic AEs were reported in >3% of patients: hematological AEs (15%) and fatigue (4%).
8eea62084ca7e541d918e823422bd82e Conclusion
The study met its primary endpoint of significant extension of survival for previously untreated mesothelioma patients. Secondary efficacy endpoints were also improved compared to historical control. The study demonstrated no safety concerns for the combination of TTFields to the thorax together with standard chemotherapy. These results support the addition of TTFields to standard chemotherapy in the treatment of first-line malignant pleural mesothelioma.
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-92 - “All-In-One” Window: A New Way of Looking at Chest CT Studies in Thoracic Oncology (ID 12427)
16:45 - 18:00 | Author(s): Jan P Van Meerbeeck
- Abstract
Background
Historically, CT studies are always viewed in several window settings, optimized to evaluate specific anatomic structures and regions (mediastinal, lung, bone and vascular window). A newly developed image processing technique fuses these conventional windows into a single “all-in-one” window. This new window is specifically designed for comparison and follow-up of CT studies in oncology. The purpose of this study is to compare lesion detection on this “all-in-one” window versus conventional window settings.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this retrospective study, 50 consecutive thoracic oncology chest CT examinations, containing 417 documented lesions and features, were reviewed by 6 radiologists, subdivided into 2 groups of 3 radiologists each, with similar levels of expertise in each group (experienced, junior and radiology resident). All scans were reviewed in conventional window settings (as in routine daily practice), by one group and in the “all-in-one” window by the other group. Lesions were listed as ‘missed’ when they were not seen by at least two out of three observers and as ‘well diagnosed’ when seen by at least two out of three observers.
4c3880bb027f159e801041b1021e88e8 Result
Out of the 417 lesions, 68 lesions were missed: 21 on the “all-in-one” window, 30 on conventional views and 17 on both views. Statistical analysis with linear mixed model showed that use of the “all-in-one” window did not result in an increase of missed lesions (p=1). Conversely, we found a tendency towards better lesion detection on the “all-in-one” window, though not strongly significant (p=0.07). Inter-observer agreement in both groups was similar (p=0.462).
8eea62084ca7e541d918e823422bd82e Conclusion
Our proposed new way of looking at chest CT images seems promising. In this study, we showed that lesion detection on a single "all-in-one" window is at least as good as on multiple conventional window settings. In further research, we will investigate the effect on lesion measurement and characterization.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.06-25 - Combined Immune Checkpoint Blockade in Malignant Pleural Mesothelioma: In Vivo Validation of in Vitro Results (ID 12075)
16:45 - 18:00 | Presenting Author(s): Jan P Van Meerbeeck
- Abstract
Background
Till today, human malignant pleural mesothelioma (MPM) remains an aggressive cancer with a poor prognosis due to the limited impact on overall survival of the current treatments. Data from us and others about the presence of the immune checkpoint-related molecules PD-1, PD-L1, TIM-3 and LAG-3 in MPM lay the basis to evaluate their suitability as immunotherapeutic targets. Two clinical trials that investigated PD-1 and PD-L1 inhibition in mesothelioma (KEYNOTE-28, JAVELIN trial) have shown promising results with room for improvement. It is of great interest to investigate the effect of combined treatments and compare them to stand-alone treatment to select the best therapeutic strategy for MPM.
a9ded1e5ce5d75814730bb4caaf49419 Method
Human cell lines representative for the epithelioid (NCI-H2818 and NCI-H2795) and sarcomatoid (NCI-H2731) subtypes of MPM were placed in allogeneic co-cultures with healthy donor peripheral blood mononuclear cells. The co-cultures were treated with the following immune checkpoint blocking antibodies: anti PD-1 (Nivolumab®, BMS) or anti PD-L1 (Durvalumab®, AstraZeneca) in combination with anti TIM-3 or anti LAG-3. Supernatant was collected and enzyme-linked immunosorbent assays and multiplex electrochemo-luminescence were used to look at the secretion of 7 cytokines, being IFNg, IL-2/5/6/10, IL-1b and TNF-a, as well as the enzyme granzyme B. Statistical analysis was done to investigate the differences between the treatment conditions.
4c3880bb027f159e801041b1021e88e8 Result
Treatment with immune checkpoint blockers as monotherapy or in combination resulted in a significant increase in the secretion of granzyme B and the cytokines IFNg, IL-2, IL-5 and IL-10. Although the increased secretion was not always statistically significant for all 3 MPM cell lines of the two subtypes, the same trends were observed among them. Interestingly, highest concentrations of granzyme B and these 4 cytokines were noticed for monotherapy treatment with anti PD-1, anti PD-L1 or either of these antibodies with anti TIM-3. In vivo investigation of PD-1 or PD-L1 blockade in combination with TIM-3 or LAG-3 blockade is currently ongoing to validate our in vitro results.
8eea62084ca7e541d918e823422bd82e Conclusion
Our data show that treatment with anti PD-1, anti PD-L1 or their respective combination with anti TIM-3 resulted in the highest secretion of cytokines and granzyme B, suggesting that these treatments stimulate the antitumor response the most. In vivo experiments are currently ongoing for validation.
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P2.06-36 - EORTC 1205: Randomized Phase II Study of Pleurectomy/Decortication Preceded or Followed by Chemotherapy in Early Stage MPM (ID 11962)
16:45 - 18:00 | Presenting Author(s): Jan P Van Meerbeeck
- Abstract
Background
Case series show a prolonged survival in resectable malignant pleural mesothelioma (MPM) with a combined modality approach of surgery and chemotherapy.
Extrapleural pneumonectomy is the most commonly used surgical procedure in MPM, but is associated with a significant morbidity; the MARS trial (Treasure, Lancet Oncol 2011) suggests no outcome benefit and a possible harm to the patient.
Retrospective studies suggest a better outcome with lung sparing resection (extended pleurectomy/decortication, e-P/D), but the procedure lacks uniformity and standardization. The optimal sequence of surgery and chemotherapy, the latter given either adjuvant or neo-adjuvant has not yet been determined.
a9ded1e5ce5d75814730bb4caaf49419 Method
EORTC 1205 is a phase II, randomized (1:1) multi-centre trial comparing both approaches. Primary end-point is the successful completion of the multimodality treatment within 20 weeks. Secondary end-points are PFS, OS, treatment-failure-free survival (TFFS), toxicity/safety, operative mortality/morbidity and surgical quality and uniformity indicators.
Patients with pathologically proven malignant pleural mesothelioma of all histological subtypes, early stage (cT1-3 N0-2 M0 according to TNM 7), WHO-PS 0-1 and fit for chemotherapy and surgery are eligible.
No previous treatment, including prophylactic track irradiation, is allowed, except for diagnostic thoracoscopy with talc pleurodesis, which must be performed before randomization.
Patients are randomized between arm A - immediate surgery (extended pleurectomy/decortication), followed by 3 cycles of cisplatin 75 mg/m² plus pemetrexed 500 mg/m² on day 1 q3w, or arm B - deferred surgery, preceded by 3 cycles of chemotherapy.
4c3880bb027f159e801041b1021e88e8 Result
Currently 4 of 6 planned sites have opened and 10 patients have been randomized in 2 centres.
8eea62084ca7e541d918e823422bd82e ConclusionArm A (n=5)
Arm B (n=5)
Male/female
4/1
4/1
Median age
59.4 years [54.6-76.9]
67.1 years [58.8-69.1]
Median PS
1 [0-1]
0 [0-1]
Stage I/II/III
3/2/0
3/0/2
EORTC 1205 addresses the issue of optimally sequencing chemotherapy and e-P/D and will rigorously record the quality of the latter in a multicentre setting. Accrual is ongoing according to expectation. Updated interim results will be presented at the WCLC meeting.
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