PIET OST

OLIGOMETASTASESPicking the finest cherries?

DEPARTMENT OF RADIATION ONCOLOGY

DISCLOSURE & DISCLAIMER

An honorarium is provided by Accuray for this presentation

The views expressed in this presentation are those of the presenters and do not necessarily reflect the views or policies of Accuray Incorporated or its subsidiaries. No official endorsement by Accuray Incorporated or any of its subsidiaries of any vendor, products or services contained in this presentation is intended or should be inferred.

Advisory Role: Ferring Pharmaceuticals (Inst), Bayer AG (Inst)Research Funding: Merck (Inst)Travel, Accommodations, Expenses: Ipsen, Ferring Pharmaceuticals

BIOLOGY AND DEFINITIONS

METASTATIC SOLID TUMORS = PALLIATIVE TREATMENT?

Metastases from solid tumors are regarded as representative of disseminated cancer and are not considered curable, with the rare

exception, such as germ cell tumors.

BIOLOGICAL DEFINITION

5

Tumors early in the chain of progression may havemetastases limited in number and location because thefacility for metastatic growth has not been fullydeveloped and the site for such growth is restricted.

Implication: metastatic disease may be cured withmetastasis-directed therapy.

Hellman & Weichselbaum, 1995

BIOLOGICAL RATIONALE FOR METASTASIS-DIRECTED THERAPY

If metastases are able to metastasize and systemic therapy inducesmore resistant and lethal clones, the addition of local therapy

directed at metastases might delay lethal disease progression…

Reyes et al. Oncotarget 2015

REMARK

There is NO universal “Oligometastases” definition

SBRT FOROLIGOMETASTASES

EARLY RESULTS

SYSTEMATIC REVIEW: NON-LIVER, NON-LUNG

Tree et al. Lancet Oncol 2012

OLIGOMETASTASES: A HYPE?

11

THE EVIDENCE

SURVEILLANCE OR MDT: PHASE II RCT

13

Eligibility:• Up to 3 metastases at time of

recurrence, excluding localrelapse

Primary endpoint: • time to ADT

• Symptoms• Local progression• Polymetastatic progression

Metastasis-directed therapy:• SBRT (30Gy in 3 fr) or surgery

55% Nodal45% Bone

55% Nodal45% Bone

Ost et al. JCO in press

BIOCHEMICAL PROGRESSION

14

Surveillance: 35% of pts have a PSA declineMDT: 75% of pts have a PSA decline

Ost et al. JCO in press

TIME TO PALLIATIVE ADT

15

ITT: median ADT-free survival 13 months vs 21 months HR: 0.60 [95% CI: 0.31 – 1.13], log-rank p=0.11

Table 2: indications for starting androgen deprivation therapy

Surveillance (n=31)

Metastasis-directed therapy (N=31)

Not started yet 6 (19%) 12 (39%)Polymetastatic progression 16 (55%) 19 (61%)Local progression 6 (23%) 0 (0%)Symptomatic progression 3 (10%)* 0 (0%)* Two patients with symptomatic progression also showed local and polymetastatic progression

Ost et al. JCO in press

TOXICITY AND QOL

16

• 17% grade I toxicity with • No grade 2 or higher toxicity• No clinically significant decline in

QOL scores over time, • No QOL difference between

arms

Ost et al. JCO in press

LOCAL CONSOLIDATIVE THERAPY VERSUS MAINTENANCE THERAPY OR OBSERVATIONFOR PATIENTS WITH OLIGOMETASTATIC NON-SMALL-CELL LUNG CANCER WITHOUT PROGRESSION AFTER FIRST-LINE SYSTEMIC THERAPY

Eligibility:• NSCLC with up to 3 mets not

including the primary after first line systemic therapy

Primary endpoint:• Progression-free survival

Local therapy:• hypofractionated RT or SBRT: 48%• Surg+RT: 24% • Chemo-radiotherapy 8%• Hypo-fractionated radiotherapy

+chemoradiotherapy: 12% • Surg to all sites: 4%

- Gomez et al. Lancet Oncol 2016

PROGRESSION-FREE SURVIVAL

Median PFS • 4 vs 12 mo • (HR 0·35 p =

0.0054)

- Gomez et al. Lancet Oncol 2016

NEW LESION-FREE SURVIVAL

- Gomez et al. Lancet Oncol 2016

Median time• 5.7 vs 12 mo • (HR 0·35, p =

0.0497)

CONSOLIDATIVE RADIOTHERAPY FOR LIMITED METASTATIC NON–SMALL-CELL LUNG CANCER: A PHASE 2 RANDOMIZED CLINICAL TRIAL

Iyengaret al. JAMA Oncol 2017

Eligibility:• NSCLC with up to up to 6 sites of

extracranial disease (includingprimary) with no more than 3 sites in the liver or lung after first line systemic therapy

Primary endpoint:• Progression-free survival

Radiotherapy:• 1 fraction: 21-27 Gy• 3 fractions: 26.5-33 Gy• 5 fractions: 30-37.(Gy

PROGRESSION-FREE SURVIVAL

Median PFS:• 3.5 mo (maintenance alone) vs 9.7

mo (SAbR-plus- maintenance)

• HR: 0.304; (95% CI, 0.1-0.8; P = .01)

TAKE HOME MESSAGE

The first evidence of local therapy for“Oligometastases” is positive!

CONCLUSION

CONCLUSION The oligometastatic state exists.

First clinical trial results are promising

How to combine metastasis-directed therapy with systemictherapy?

Trials are coming: SABR-COMET NCT 01446744, ORIOLE, CORE

NCT02759783 and SARON NCT02417662, PulMiCC,…

OLIGOCARE: OBSERVATIONAL BASKET STUDY

Prof. Dr. Piet OstRadiation oncologistSenior Clinical Investigator of the Research Foundation

Dept of Radiation Oncology

E piet.ost@ugent.be

@piet_ost

“To truth only a brief celebration of victory is allowedbetween the two long periods during which it iscondemned as paradoxical, or disparaged as trivial.”

- Arthur Schopenhauer -