Highlights WCLC, ASCO, ESMO 2019

Prof. Dirk De Ruysscher, MD, PhDRadiation OncologistMaastro Maastricht University Medical CenterUniversity MaastrichtThe Netherlands

Conflict of Interest

Institutional financial interests:

Research grant: Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, Philips, Olink

Advisory board: Bristol-Myers Squibb, Celgene, Merck/Pfizer, Roche/Genentech, AstraZeneca, MSD, Seattle genetics

Non-financial interests (advice):

NOXXON, MOLOGEN

Leadership roles:

European Thoracic Oncology Platform (ETOP)

European Organisation for Research and Treatment of Cancer (EORTC)

European Society for Therapeutic Radiology and Oncology (ESTRO)

International Association for the Study of Lung Cancer (IASLC)

Nederlandse Vereniging voor Radiotherapie en Oncologie (NVRO)

Corporate presentatie Maastricht UMC+ (titel presentatie)

Naam spreker (optioneel)

Functie spreker (optioneel)

Titel van de presentatie

OnderwerpregelPresentatie Prof. Dr. Jan Jansen

PCI for radically treated non-small cell lung cancer: a meta-analysis using updated individual patient data of randomized trials

Witlox WJA1, De Ruysscher, DKM2, Lacas, B3, Le Pechoux, C4, Pignon, J-P3, Sun, A5, Wang, S-Y6, Hu, C7,8, Redman, M9, van der Noort, V10, Li, N11, Guckenberger, M12, van Tinteren, H10, Groen, HJM13, Joore, MA1,14, Ramaekers, BLT1.

1. Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre (MUMC), The Netherlands.

2. Department of Radiation Oncology (Maastro clinic), Maastricht University Medical Center+, GROW Research Institute, Maastricht, The Netherlands.

3. Biostatistics and Epidemiology Unit, INSERM U1018, Gustave Roussy, Paris-Saclay University, Villejuif, France.

4. Department of Radiation Oncology, Gustave Roussy, Paris-Saclay University, Villejuif, France.

5. Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

6. Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

7. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.

8. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.

9. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

10. Department of Biometrics, Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.

11. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.

12. Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

13. Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

14. Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.

ResultsCorporate presentatie | stafdienst Communicatie | maart 2011 | November 22, 2019 4

Willem Witlox

PACIFIC: 50 % reductie hersenmetastasen

New Lesion Site*

Durvalumab (N=476)

Placebo (N=237)

Any new lesion, n (%) 107 (22.5) 80 (33.8)

Lung 60 (12.6) 44 (18.6)

Lymph nodes 31 (6.5) 27 (11.4)

Brain 30 (6.3) 28 (11.8)

Liver 9 (1.9) 8 (3.4)

Bone 8 (1.7) 7 (3.0)

Adrenal 3 (0.6) 5 (2.1)

Other 10 (2.1) 5 (2.1)

Antonia et al. New Engl J Med 2018

NVALT-28: Durvalumab and low-dose (15 Gy/ 10 fr) Prophylactic Cranial Irradiation (PCI) versus durvalumaband observation in radically treated patients with stage III non-small cell lung cancer: A phase III randomized study Primary objective

To evaluate whether the addition of PCI to durvalumab after concurrent chemo-radiotherapy for stage III

NSCLC reduces the incidence of brain metastases.

Secondary objectives

Key secondary objective: to evaluate what the effect is on neurocognitive functioning (HVLT-R) with the

addition of PCI to durvalumab.

N=170

E. Gkika, Department of Radiation Oncology, University Medical Center Freiburg, Germany

Imaging-guided target volume reduction in radiotherapy of

lung cancer: the prospective randomized multinational

PET-Plan trial

Ursula NESTLE1,2, T. SCHIMEK-JASCH2, S. KREMP3, A. SCHAEFER-SCHULER4, A. KÜSTERS1, M. TOSCH5, T. HEHR6, S.M. ESCHMANN7, Y. BULTEL8, P. HASS9, J. FLECKENSTEIN3, A. THIEME10, M. STOCKINGER11, M. MIEDERER11, M. BECK12, G.

HOLL13, H. RISCHKE2, E. GKIKA2, S. ADEBAHR2, J. KOENIG14, A. GROSU2.1KLINIKEN MARIA HILF GMBH, DEPARTMENT OF RADIATION ONCOLOGY, MÖNCHENGLADBACH, D, 2UNIVERSITY HOSPITAL FREIBURG, DEPARTMENT FOR RADIATION ONCOLOGY, D. 3UNIVERSITY HOSPITAL SAARLAND,

DEPARTMENTS FOR RADIATION ONCOLOGY and 4NUCLEAR MEDICINE, D., 5HELIOS KLINIKUM WUPPERTAL, DEPARTMENT FOR NUCLEAR MEDICINE, D., 6MARIENHOSPITAL STUTTGART, DEPARTMENTS FOR RADIATION ONCOLOGY and 7NUCLEAR MEDICINE, STUTTGART, D., 8MUTTERHAUS DER BOROMAEERINNEN, DEPARTMENT FOR RADIATION ONCOLOGY, TRIER, D., 9UNIVERSITY HOSPITAL MAGDEBURG, DEPARTMENT FOR RADIATION ONCOLOGY, D.,

10CHARITE UNIVERSITY HOSPITAL, DEPARTMENT FOR RADIATION ONCOLOGY, BERLIN, D., 11UNIVERSITY HOSPITAL MAINZ, DEPARTMENT FOR RADIATION ONCOLOGY and NUCLEAR MEDICINE, D., 12GEMEINSCHAFTSPRAXIS FUER STRAHLENTHERAPIE, NEUMUENSTER, D., 13HELIOS KLINIKEN SCHWERIN, DEPARTMENT FOR NUCLEAR MEDICINE, D., 14UNIVERSITY MEDICAL CENTER, MAINZ, INSTITUTE OF MEDICAL BIOSTATISTICS, EPIDEMIOLOGY AND

INFORMATICS, D.

Hypothesis (2006):

… in locally advanced NSCLC

dose escalated radiochemotherapy

with 18-FDG-PET based RT-planning

avoiding ENI

will show at least similar outcome

as compared to conventional planning

gefördert durch die

Deutsche KrebshilfePET - Plan

All patients: PET-based CTV

- primary tumor (PET-GTV + 3 mm to CTV)

- FDG-positive LN-stations (anatomical, Chapet)

• Arm A

expanded PET-CTV (+ atelectasis (3cm), + CT-positive LNS)

subject to isotoxic dose escalation

elective LN volumes (10%-risk-areas)

50 Gy/ 2 Gy

• Experimental arm B

PET-Volume only

subject to isotoxic dose escalation

Escalated total reference dose

60

62

64

66

68

70

72

74 Arm A Arm B

Odds ratio 2.35(95% CI 1.27-4.35), p=0.007

Means ± SD 65.3 ± 5.3 67.3 ± 5.2, p=0.016

Median [Quartiles] 64 [60, 70] 66 [63.5, 74] p=0.012

≥66 39 59

≤64 45 294 310 7

11

18

3 410 11

1 314 23

G

y

18

31 19

ToxicityTreatment-related

toxicity, n (%)

Arm A

Conventional treatment planning

n=99

Experimental arm B

FDG-PET-based treatment planning

n=105

Any Grade ≥ Grade 3 Any Grade ≥ Grade 3

Acute toxicity (≤ 90 days after start of radiotherapy); CTCAE 4.0

Esophagus 70 (71) 16 (16) 70 (67) 17 (16)

Dyspnea 27 (27) 6 (6) 37 (35) 8 (7)

Pneumonitis 9 (9) 1 (1) 11 (10) 1 (1)

Cardiac toxicity 12 (12) 3 (3) 12 (11) 5 (5)

Dermatitis (local)37 (37)

3 (3)35 (33)

0 (0)

Late toxicity (> 91 days after start of radiotherapy); RTOG/EORTC

Esophagus 13 (13) 2 (2) 20 (19) 1 (1)

Lung 60 (61) 12 (12) 59 (56) 11 (10)

Heart 17 (17) 3 (3) 18 (17) 5 (5)

Skin 7 (7) 0 (0) 7 (7) 0 (0)

Subcutaneous 0 (0) 0 (0) 1 (1) 0 (0)

Spinal cord 3 (3) 0 (0) 2 (2) 0 (0)

Blood:

Hemoglobin 5 (5) 0 (0) 7 (7) 2 (2)

Leucocytes 3 (3) 1 (1) 3 (3) 1 (1)

Thrombocytes 0 (0) 0 (0) 2 (2) 0 (0)

Primary Endpoint Cumulative incidence of locoregional progression (pp)

Arm A

Experimental arm

B

0 1 2 3 4 5 6

0.0

0.2

0.4

0.6

0.8

1.0

88 59 52 44 40 39 3484 48 37 34 32 28 25

HR 0.57

95% CI 0.30-1.06

LPP@2y 39% (Arm A)

vs 20% (Arm B)

p=0.078 two sided

Years from randomisation

Overall survival (pp population)

0 2 4 6

0.0

0.2

0.4

0.6

0.8

1.0

Zeit in Jahren

Wa

hrs

che

inlic

hke

itÜberleben

88 55 33 17 10 8 1

84 59 35 25 13 9 6 2

Arm A

Arm B

Years from randomisation

Pro

ba

bilit

yo

fs

urv

iva

l

HR 1.21

95% CI 0.79-1.84

OS@2y 57% (Arm A)

vs 54% (Arm B)

p=0.38

NRG-LU001

Randomized phase II trial of concurrent

chemoradiotherapy (CRT) +/- metformin in locally

advanced Non-Small Cell Lung Cancer (NSCLC).

Heath Skinner, Chen Hu, Theodoros Tsakiridis, Rafael Santana-Davila, Bo Lu, Jeremy J Erasmus,

Anthony J Doemer, Gregory M Videtic, James Coster, Alex Xuexhong Yang, Richard Y Lee, Maria

Werner-Wasik, Philip E Schaner, Steven E McCormack, Benjamin T Esparaz, Ronald C McGarry, Jose

Bazan, Timothy Struve and Jeffrey D Bradley

WCLC

September 2019

• To determine whether metformin HCL added to chemo-

radiotherapy can improve progression-free survival (PFS)

in patients with locally advanced NSCLC

• Study was designed to detect a 15% improvement in 12

month PFS (from 50 to 65%)

NRG LU001: Primary Objective

NRG LU001: Progression free survivalAll Patients (ITT) Metformin Per Protocol

60.4%

NRG LU001: Overall survivalAll Patients (ITT) Metformin Per Protocol

NRG LU001: Loco-regional failureAll Patients (ITT) Metformin Per Protocol

NRG LU001: Distant metastasisAll Patients (ITT) Metformin Per Protocol

Joint effort ESMO and ESTROThe following items of importance for further improvement of supportive care:

• smoking cessation

• nutrition before and during CCRT (including treatment and prevention of anorexia)

• physical exercise before and during CCRT

• prevention and treatment of acute esophagitis and dysphagia

• treatment of cough and dyspnea

• treatment of skin reactions

• treatment of fatigue

• prophylaxis of nausea and emesis

• prevention, diagnosis and treatment of cardiac disease and damage

• optimization of radiotherapy techniques and chemotherapy adjustments to reduce toxicity in the era of immune therapy.