ESMO Supporter 2018

Displaying One Session

Hall A2 - Room 18 Proffered Paper session
Date
21.10.2018
Time
16:30 - 18:10
Location
Hall A2 - Room 18
Chairs
  • Fortunato Ciardiello (Napoli, IT)
  • Josep Tabernero (Barcelona, ES)
Presidential Symposium 2 Proffered Paper session

Session DOI

Lecture Time
16:30 - 16:30
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
21.10.2018
Time
16:30 - 18:10
Presidential Symposium 2 Proffered Paper session

LBA4 - Effects of Abiraterone Acetate plus Prednisone/Prednisolone in High and Low Risk Metastatic Hormone Sensitive Prostate Cancer

Presentation Number
LBA4
Lecture Time
16:30 - 16:45
Speakers
  • Alex P. Hoyle (Manchester, GB)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
21.10.2018
Time
16:30 - 18:10

Abstract

Background

Abiraterone acetate plus prednisone/prednisolone (AAP) is licenced in the EU for use in “high risk” newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) based on results of the LATITUDE trial. However, the STAMPEDE “AAP comparison” did not suggest a differential effect, with similar benefits in M0 & M1 patients (pts). We evaluate heterogeneity of AAP effect on overall (OS) & failure-free-survival (FFS) in pts with LATITUDE defined high & low risk M1 disease treated with androgen deprivation therapy (ADT) or ADT + AAP, randomised within the STAMPEDE trial.

Methods

Staging scans were evaluated centrally for M1 pts randomized to ADT (Arm A) or AAP (Arm G) within trial. Following review, pts were classified as low or high risk according to the LATITUDE criteria. The primary study endpoint was overall survival (OS) & the secondary endpoint was failure-free survival (FFS). Further exploratory analysis evaluated skeletal related events (SRE), progression free survival (PFS) & prostate cancer specific survival (PCSS). Secondary differential analysis by tumor volume (high/low) was done using the criteria defined in CHAARTED.

Results

901 of 990 eligible M1 pts were evaluable. Median age 67yr, median PSA 96ng/ml, median follow up 42mth. 473 pts were high risk & 428 low risk according to LATITUDE criteria. AAP treated pts had clinically & statistically significant OS improvements in both high (HR: 0.54, 95% CI [0.41-0.70]; p<0.001) & low (HR: 0.66, 95% CI [0.44-0.98]; p=0.041) risk groups. Pts receiving AAP also benefited from prolonged FFS within both high (HR: 0.31, 95% CI [0.25-0.39]; p<0.001) & low risk groups (HR: 0.238, 95% CI [0.17-0.33]; p<0.001). No evidence of heterogeneity between risk groups was found in OS or FFS (interaction p-value, p=0.385 & p=0.294 respectively). Further analyses incorporating the alternative CHAARTED volume definition was done with similar outcomes.

Conclusions

Men with primary mHSPC treated with AAP plus ADT had a significant increase in OS & FFS compared to those receiving ADT alone, irrespective of risk/volume sub-classification. These results show AAP treatment benefit across all mHSPC pts, irrespective of M1 risk/volume sub-stratification using conventional imaging.

Clinical trial identification

NCT00268476

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Presidential Symposium 2 Proffered Paper session

Invited discussant

Lecture Time
16:45 - 16:55
Speakers
  • Karim Fizazi (Villejuif, FR)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
21.10.2018
Time
16:30 - 18:10
Presidential Symposium 2 Proffered Paper session

LBA5_PR - Radiotherapy (RT) to the primary tumour for men with newly-diagnosed metastatic prostate cancer (PCa): Survival results from STAMPEDE (NCT00268476)

Presentation Number
LBA5_PR
Lecture Time
16:55 - 17:10
Speakers
  • Chris C. Parker (Sutton, GB)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
21.10.2018
Time
16:30 - 18:10

Abstract

Background

Local treatment of the prostate might not only improve local control but also slow progression of metastatic disease. We hypothesised that RT to the prostate would improve overall survival in men presenting with metastatic PCa & that survival benefit would be greater in men with lower metastatic burden.

Methods

STAMPEDE, a multi-arm multi-stage platform protocol, included a randomised phase III comparison to test this hypothesis. Standard-of-care (SOC) was lifelong androgen deprivation therapy (ADT), with early docetaxel permitted from 2016. Stratified randomisation within 12 wk on ADT allocated pts 1:1 to SOC or SOC+RT. Men allocated to RT had daily (55Gy/20f/4wk) or weekly (36Gy/6f/6wk) schedules, started ≤8wk after randomisation or docetaxel. The primary outcome measure (OM) was death from any cause; secondary OMs included failure-free survival (FFS). 90% power & 2.5% 1 sided α for hazard ratio (HR) 0.75 required ~267 control arm deaths. Analyses used Cox proportional hazards & flexible parametric models. Directionally pre-specified subgroup analysis tested effects by metastatic burden at entry.

Results

2061 men with newly-diagnosed M1 PCa were randomised Jan 2013 - Sep 2016. Randomised groups were well balanced: median age 68 yr; median PSA 97ng/ml; 18% early docetaxel; metastatic burden: 40% lower, 54% higher, 6% unknown. Prostate RT improved FFS (HR=0.76, 95%CI 0.68, 0.84) but not overall survival (HR=0.92, 95%CI 0.80, 1.06). Subgroup analysis showed improved overall survival for prostate RT in 819 men with lower metastatic burden (HR=0.68, 95%CI 0.52, 0.90) but not in 1120 men with higher metastatic burden (HR=1.07, 95%CI 0.90, 1.28). RT was well-tolerated during (5% Grd3-4 SOC+ RT) & after treatment (Grd3-4 <1% SOC, 4% SOC+RT).

Conclusions

Radiotherapy to the prostate did not improve survival for unselected patients with newly-diagnosed metastatic prostate cancer, but, in a pre-planned analysis, did improve survival in men with a lower metastatic burden. Therefore, prostate radiotherapy should be a standard treatment option for men with oligometastatic disease.

Clinical trial identification

NCT00268476

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Presidential Symposium 2 Proffered Paper session

Invited discussant

Lecture Time
17:10 - 17:20
Speakers
  • Robert Bristow (Manchester, GB)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
21.10.2018
Time
16:30 - 18:10
Presidential Symposium 2 Proffered Paper session

LBA6_PR - JAVELIN Renal 101: a randomized, phase 3 study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC)

Presentation Number
LBA6_PR
Lecture Time
17:20 - 17:35
Speakers
  • Robert J. Motzer (New York, US)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
21.10.2018
Time
16:30 - 18:10

Abstract

Background

In a phase 1b trial, 1L A + Ax had encouraging antitumor activity for patients (pts) with aRCC (Lancet Oncol. 2018;19:451).

Methods

Eligible pts with clear-cell aRCC, ECOG ≤ 1, and no prior systemic therapy were randomized 1:1 (stratified by ECOG and geographic region) to receive A 10 mg/kg IV Q2W + Ax 5 mg PO BID in 6-wk cycles or S 50 mg PO QD on schedule 4/2; all prognostic risk groups were included. Primary endpoints were progression-free survival (PFS; by blinded independent central review [BICR] per RECIST v1.1) and overall survival (OS) in pts with PD-L1+ tumors (≥ 1% of immune cells). Secondary endpoints included PFS by BICR and OS irrespective of PD-L1 expression, objective response (OR), and safety.

Results

As of 20 Jun 2018, 886 pts were randomized (A + Ax: N = 442; S: N = 444); of these, 21%/62%/16% had favorable/intermediate/poor IMDC risk criteria (not reported in < 1%). In 560 pts (63.2%) with PD-L1+ tumors, median PFS was 13.8 vs 7.2 mo in A + Ax vs S arms, respectively (HR = 0.61; p < .0001; Table). Median PFS in pts irrespective of PD-L1 expression was 13.8 vs 8.4 mo (HR = 0.69; p = .0001). PFS and OR results favored A + Ax in pts irrespective of PD-L1 expression and in all MSKCC/IMDC prognostic risk groups. OS data were immature at data cutoff (< 16% of pts with events). In A + Ax vs S arms, grade ≥3 treatment-emergent adverse events occurred in 71.2% vs 71.5% of pts and led to discontinuation of any study drug in 22.8% vs 13.4%; deaths due to study treatment toxicity occurred in 0.7% vs 0.2% of pts.

Pts with PD-L1+ tumors

A + Ax (N = 270)

S (N = 290)

PFS per BICR (primary endpoint)

Median (95% CI), mo

Stratified hazard ratio (95% CI); 1-sided p value

13.8 (11.1, not estimable)

7.2 (5.7, 9.7)

0.61 (0.475, 0.790); p < .0001

Confirmed objective response rate per BICR

Objective response rate (95% CI), %

Stratified odds ratio (95% CI); 1-sided p value

55.2 (49.0, 61.2)

25.5 (20.6, 30.9)

3.732 (2.532, 5.371); p < .0001

Pts irrespective of PD-L1 expression

A + Ax (N = 442)

S (N = 444)

PFS per BICR

Median (95% CI), mo

Stratified hazard ratio (95% CI); 1-sided p value

13.8 (11.1, not estimable)

8.4 (6.9, 11.1)

0.69 (0.563, 0.840); p = .0001

Confirmed objective response rate per BICR

Objective response rate (95% CI), %

Stratified odds ratio (95% CI); 1-sided p value

51.4 (46.6, 56.1)

25.7 (21.7, 30.0)

3.098 (2.300, 4.148); p < .0001

Conclusions

This randomized phase 3 trial met its primary objective of significantly improving PFS in pts with PD-L1+ aRCC treated with A + Ax vs S. PFS and OR benefit was also observed in pts irrespective of PD-L1 expression and across all prognostic risk groups. The safety profiles were consistent with those of prior studies of each drug. These results support A + Ax as a potential new 1L standard-of-care for pts with aRCC.

Clinical trial identification

Clinical Trial Number: NCT02684006

Editorial Acknowledgement

Medical writing support was provided by ClinicalThinking Inc., Hamilton, NJ, USA.

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Presidential Symposium 2 Proffered Paper session

Invited discussant

Lecture Time
17:35 - 17:45
Speakers
  • Viktor Grünwald (Essen, DE)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
21.10.2018
Time
16:30 - 18:10
Presidential Symposium 2 Proffered Paper session

LBA7_PR - Maintenance olaparib following platinum-based chemotherapy in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA1/2 mutation (BRCAm): Phase III SOLO1 trial

Presentation Number
LBA7_PR
Lecture Time
17:45 - 18:00
Speakers
  • Kathleen N. Moore (Oklahoma City, US)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
21.10.2018
Time
16:30 - 18:10

Abstract

Background

Pts with newly diagnosed advanced OC are treated with cytoreductive surgery and platinum-based chemotherapy. Most relapse within the first 3 years and have further chemotherapy, but once relapsed are largely not curable. SOLO1 (NCT01844986) is the first Phase III trial to evaluate PARP inhibitor (olaparib [Lynparza®]) maintenance therapy after platinum-based chemotherapy in newly diagnosed advanced OC with a BRCAm.

Methods

SOLO1 is a randomized, controlled, double-blind trial. Eligible pts had newly diagnosed, FIGO stage III–IV, high-grade serous or endometrioid ovarian, primary peritoneal and/or fallopian tube cancer with a BRCAm, had received platinum-based chemotherapy and were in clinical complete or partial response. Pts were randomized 2:1 to olaparib tablets 300 mg bd or placebo. The primary endpoint was investigator-assessed progression-free survival (PFS; modified RECIST v1.1).

Results

Of 391 randomized pts, 260 received olaparib and 130 placebo (one pt did not receive placebo). Median follow-up was 41 months. Baseline characteristics were well balanced. Primary PFS analysis showed a significant 70% reduction in the risk of progression or death with olaparib versus placebo (Table). PFS sensitivity analyses, second PFS and time to first subsequent therapy or death support the primary analysis. Overall survival data are immature.

Median, months HR (95% CI)
P value
Olaparib
(N=260)
Placebo
(N=131)
Between-group
difference
PFS, investigator
assessed
(51% maturity)
NR 13.8 NC 0.30 (0.23–0.41)
P<0.0001
PFS, BICR*
(38% maturity)
NR 14.1 NC 0.28 (0.20–0.39)
P<0.0001
TFST 51.8 15.1 36.7 0.30 (0.22–0.40)
P<0.0001
PFS2
(31% maturity)
NR 41.9 NC 0.50 (0.35–0.72)
P=0.0002
*Sensitivity analysis using BICR
BICR, blinded independent central review; HR, hazard ratio; NC, not calculable; NR, not reached; PFS, progression-free survival; PFS2, time from randomization to second progression or death; TFST, time to first subsequent therapy or death

Adverse events were mostly low grade. The most common grade ≥3 toxicities with olaparib were anaemia (22%) and neutropenia (8%). Olaparib dose reductions, interruptions and discontinuations occurred in 28%, 52% and 12%, respectively. There was no change from baseline in health-related quality of life scores with olaparib.

Conclusions

Maintenance olaparib led to a substantial, unprecedented improvement in PFS, with an estimated difference in median PFS for olaparib versus placebo of approximately 3 years.

Clinical trial identification

ClinicalTrials.gov NCT01844986, July 2018

Editorial Acknowledgement

Editorial assistance was provided by Gillian Keating, Mudskipper Business Limited, funded by AstraZeneca and Merck & Co., Inc..

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Presidential Symposium 2 Proffered Paper session

Invited discussant

Lecture Time
18:00 - 18:10
Speakers
  • Jonathan A. Ledermann (London, GB)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
21.10.2018
Time
16:30 - 18:10