Displaying One Session

Valencia Auditorium (Hall 5) Poster Discussion session
Date
29.09.2019
Time
10:30 - 11:30
Location
Valencia Auditorium (Hall 5)
Chairs
  • Sven Mahner (Munich, Germany)
  • Robert L. Coleman (Houston, TX, United States of America)
Poster Discussion – Gynaecological cancers Poster Discussion session

995PD - Time to second progression (PFS2) and second subsequent therapy (TSST) for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) treated with maintenance (mt) olaparib (ola): Phase III SOLO1 trial (ID 4350)

Presentation Number
995PD
Lecture Time
10:30 - 10:30
Speakers
  • Ana Oaknin (Barcelona, Spain)
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30

Abstract

Background

SOLO1 (NCT01844986; GOG-3004) pts with newly diagnosed, advanced OC and a BRCAm treated with mt ola had a substantial progression-free survival benefit vs placebo (pbo) (HR 0.30 [95% CI 0.23–0.41], P < 0.001; Moore et al. NEJM 2018). The impact of first line use of PARP inhibitors (PARPi) on subsequent therapy is of clinical interest. Secondary objectives included PFS2 and TSST, which indicate the effect of treatment beyond first progression.

Methods

Pts were randomized 2:1 to ola 300 mg bid or pbo for up to 2 years or until disease progression. After first progression, PFS2 was assessed every 12 weeks (radiological, CA125 or clinical progression).

Results

There were 121 PFS2 events (HR 0.50, 95% CI 0.35–0.72, median PFS2 was not reached (NR) [ola] vs 41.9 months [m; pbo]). Median TSST was NR (ola) vs 40.7 m (pbo; HR 0.45, 95% CI 0.32–0.63). Based on Kaplan-Meier estimates, at 36 m, the proportions of ola pts free from second progression or second therapy were 15 and 18 percentage points higher respectively, than the proportions of pbo pts (Table).

Kaplan-Meier estimates of pts free from second disease progression (%)
Kaplan-Meier estimates of pts free from second subsequent therapy (%)
Time from randomization (m)Olaparib n = 260Placebo n = 131Olaparib n = 260Placebo n = 131
1296959795
2486778569
3675607456

Of 198 pts who progressed, 91/102 in the ola arm and 94/96 in the pbo arm had a subsequent therapy or therapies: the most common therapies were platinum (plat)-based chemotherapy (chemo) (n = 58 [64%] vs n = 50 [53%]), including plat with bevacizumab (bev) (n = 22 [24%] vs n = 15 [16%]); PARPi, including plat followed by PARPi (n = 20 [22%] vs n = 49 [52%]); and non-plat chemo (excluding regimens with bev) (n = 35 [38%] vs n = 26 [28%]). In the ola arm, 10 pts had ola as part of their first subsequent therapy (9 had ola as mt following plat-based chemo) and 3 progressed for a second time. In the pbo arm, 44 (47%) pts who had subsequent therapy had ola outside the study.

Conclusions

Mt ola increases both PFS2 and TSST vs pbo. The benefit of mt ola in newly diagnosed OC continues beyond first progression.

Clinical trial identification

NCT01844986.

Editorial acknowledgement

Laura Smart, from Mudskipper Business, Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Legal entity responsible for the study

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Funding

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Disclosure

A. Oaknin: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Genmab. K. Moore: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Advaxis; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Immunogen; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy: Aravive; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eisai; Advisory / Consultancy: Samumed; Advisory / Consultancy: Oncomed. N. Colombo: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Pfizer. M. Friedlander: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy: Takeda; Non-remunerated activity/ies: AbbVie. A. Floquet: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Honoraria (self): Roche; Honoraria (self): PharmaMar; Honoraria (self), Advisory / Consultancy: Tesaro. A. Leary: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Biocad; Advisory / Consultancy: Seattle Genetics. G.S. Sonke: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Roche; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis. C. Gourley: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Tesaro; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Nucana; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy: Foundation One; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Sierra Oncology; Research grant / Funding (self): Novartis; Research grant / Funding (self): Aprea. S. Banerjee: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. A.M. Oza: Non-remunerated activity/ies, Steering committee: AstraZeneca; Non-remunerated activity/ies, Steering committee: Clovis Oncology; Non-remunerated activity/ies, Steering committee: Tesaro. A. González-Martín: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Tesaro; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Genmab; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: PharmaMar. C. Aghajanian: Honoraria (self): Tesaro; Honoraria (self): ImmunoGen; Honoraria (self): Clovis Oncology. E.S. Lowe: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Bloomfield: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. DiSilvestro: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro. All other authors have declared no conflicts of interest.

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Poster Discussion – Gynaecological cancers Poster Discussion session

996PD - Patient-centred outcomes with maintenance olaparib in newly diagnosed patients with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) in the phase III SOLO1 trial to support the clinical benefit of prolongation of progression-free survival (PFS) (ID 2325)

Presentation Number
996PD
Lecture Time
10:30 - 10:30
Speakers
  • Michael L. Friedlander (Randwick, Australia)
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30

Abstract

Background

In SOLO1 (NCT01844986; GOG-3004), maintenance olaparib significantly improved PFS vs placebo (HR 0.30; 95% CI 0.23–0.41; Moore et al. NEJM 2018) in patients with newly diagnosed advanced OC, a BRCAm and clinical complete or partial response after platinum-based chemotherapy. Most patients in the maintenance setting are well following first-line treatment; thus, it is important to show that extending PFS is not at the expense of decreased health-related quality of life because of toxicity. We assessed the duration of ‘good quality of life’ while on maintenance therapy based on time without significant symptoms of toxicity (TWiST) and quality-adjusted PFS (QAPFS) which both incorporate the adverse effects experienced by patients on maintenance therapy.

Methods

Patients were randomized 2:1 to olaparib tablets 300 mg bid or placebo. Patient-centred outcomes were assessed by QAPFS (product of adjusted mean estimate of the EuroQol 5D-5L single-index utility score from randomization to disease progression and mean PFS time) and TWiST (period without significant symptoms post-randomization and before disease progression or censoring for progression) in a post hoc analysis in the full analysis set.

Results

Of 391 randomized patients, 260 received olaparib and 130 placebo (one patient did not receive placebo). Mean QAPFS and TWiST improved to a clinically meaningful extent with olaparib vs placebo, with highly significant between-group improvements of at least 12 months (Table).

OlaparibPlacebo
QAPFSn = 260n = 131
Mean duration (95% CI), months29.75 (28.20–31.63)17.58 (15.05–20.18)
Between-group difference (95% CI), months12.17 (9.07–15.11)
P valueP < 0.001
TWiST*n = 260n = 131
Mean duration (95% CI), months33.15 (30.82–35.49)20.24 (17.36–23.11)
Between-group difference (95% CI), months12.92 (9.30–16.54)
P valueP < 0.001

TWiST is the time without significant symptoms of toxicity, defined as grade ≥2 nausea, vomiting or fatigue

Conclusions

There were clinically meaningful patient-centred benefits with maintenance olaparib in both QAPFS and TWiST supporting the substantial benefit of PFS improvement seen with olaparib in newly diagnosed advanced OC.

Clinical trial identification

NCT01844986 (SOLO1; GOG-3004).

Editorial acknowledgement

Gillian Keating, MBChB, from Mudskipper Business Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD).

Legal entity responsible for the study

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD).

Funding

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD).

Disclosure

M.L. Friedlander: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy: Takeda; Non-remunerated activity/ies: AbbVie. K. Moore: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Advaxis; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Immunogen; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy: Aravive; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eisai; Advisory / Consultancy: Samumed; Advisory / Consultancy: Oncomed. N. Colombo: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Pfizer. A. Oaknin: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Genmab. A. Floquet: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Roche; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Tesaro. A. Leary: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Biocad; Advisory / Consultancy: Seattle Genetics. G.S. Sonke: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self): Roche. C. Gourley: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Tesaro; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Nucana; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy: Foundation One; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Sierra Oncology; Research grant / Funding (self): Novartis; Research grant / Funding (self): Aprea. S. Banerjee: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. A. Oza: Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: Clovis Oncology; Non-remunerated activity/ies: Tesaro. A. González-Martín: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Genmab; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD. C. Aghajanian: Honoraria (self): Tesaro; Honoraria (self): ImmunoGen; Honoraria (self): Clovis Oncology. E. Lowe: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Hettle: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. E. Flood: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. DiSilvestro: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro. All other authors have declared no conflicts of interest.

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Poster Discussion – Gynaecological cancers Poster Discussion session

997PD - Validation of the geriatric vulnerability score (GVS) in older ovarian cancer (oOC) patients: An analysis from the GCIG-ENGOT-GINECO EWOC-1 study (ID 2019)

Presentation Number
997PD
Lecture Time
10:30 - 10:30
Speakers
  • Fabian Tinquaut (Saint-Priest-en-Jarez, France)
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30

Abstract

Background

The GINECO previously developed the GVS to identify geriatric vulnerability in oOC pts (Falandry, 2013). The derivation cohort was EWOT-3 database of 111 oOC pts treated with first line carboplatin. The GVS combines albumin (≥ or < 35g/l), lymphocyte (< or ≥ 1x109/L) levels, and activities of daily living (ADL; ≥ or < 6), Instrumental ADL (≥ or < 25), HADS (< or ≥ 14) scores. With a cut-off ≥3, GVS delineated a population with significantly decreased OS (HR(95%CI)=2.94 (1.79–4.84), P <.0001). EWOC-1 international study included an external validation of the GVS as a secondary endpoint.

Methods

Pts ≥70 yrs diagnosed with FIGO stage III/IV epithelial OC and no organ failure were screened for GVS. Those with GVS≥3 were proposed EWOC-1 randomized trial, evaluating 3 treatment regimens in the vulnerable pts. Other pts’ data were collected in the “EWOC-1 registry”. External validation of GVS was performed in the whole population (V1), in the EWOC-1 registry subgroup (V2), and in the subgroup of pts treated with carboplatin paclitaxel regimens (V3). Cross-validation analyses (calibration, discrimination, and performance analysis) were performed according current recommendations (Steyerber, 2014).

Results

From 12/2013 to 11/2018, 447 elderly patients were included, 120 (27%) in EWOC-1 trial and 327 in EWOC-1 registry (V1: n = 447, V2: n = 327, V3: n = 324). Patients’ cancer characteristics were similar in the validation cohorts compared to the derivation one. Median follow up was 22 mo; missing values were limited (<2%). According the maximum likelihood analysis, the risk ratio of death according GVS score in V1 was (ref=0): 1: 1.8 (p=.029); 2: 2.4 (p<.001); 3: 4.1 (p<.001); 4: 5.5 (p<.001); 5: 9.1 (p<.001). Whatever the validation cohort, GVS≥3 significantly segregated two groups with different OS (median, in mo): V1 (13.2 vs 40.8; HR = 2.8 (2.2,3.7), p<.001), V2 (11.9 vs 40.8, HR = 3.5 (2.5,4.9), p<.001); V3 (18.1 vs 43, HR = 2.6 (1.9,3.7), p<.001).

Conclusions

GVS provides a reproducible and robust prediction model of vulnerability in oOC pts, independent of geographic and historic effect (V1), as well as treatment patterns (V3), validated on an international population.

Clinical trial identification

PROTOCOL EWOC-1 - ENGOT OV-23 - 2013-000266-11.

Legal entity responsible for the study

Centre Hospitalier Lyon Sud.

Funding

Hospital Clinical Research Program (PHRC).

Disclosure

D. Lorusso: Honoraria (self), Honoraria (institution), Advisory / Consultancy: MERCK; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Clovis; Advisory / Consultancy: Immunogen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Tesaro; Officer / Board of Directors, Spouse / Financial dependant, Non-remunerated activity/ies: GCIG. A. Floquet: Advisory / Consultancy: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: Roche. O. Tredan: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): BMS; Honoraria (self): MSD. E. Pujade-Lauraine: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder /: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Clovis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time e: Tesaro; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Genmab; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Incyte; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Pfizer. C. Falandry: Honoraria (self): Leo Pharma; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self): MSD oncology; Honoraria (self): Teva; Honoraria (self): AstraZeneca; Honoraria (self): Baxter; Honoraria (self): Eisai; Honoraria (self): Janssen; Honoraria (self): Novartis; Honoraria (institution): Chugai Pharma; Honoraria (institution): Pierre Fabre; Honoraria (institution): Astellas Pharma. All other authors have declared no conflicts of interest.

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Poster Discussion – Gynaecological cancers Poster Discussion session

1190PD - Phase II study of olaparib + durvalumab (MEDIOLA): Updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC) (ID 4563)

Presentation Number
1190PD
Lecture Time
10:30 - 10:30
Speakers
  • Yvette Drew (Newcastle-upon-Tyne, United Kingdom)
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30

Abstract

Background

Olaparib (Lynparza®) is a poly(ADP-ribose) polymerase (PARP) inhibitor approved as maintenance treatment of PSR OC. MEDIOLA assessed olaparib in combination with the anti-programmed cell death ligand1 antibody, durvalumab, in germline BRCA1 and/or BRCA2 mutated (gBRCAm) PSR OC (NCT02734004). The 12-week (wk) disease control rate (DCR) = complete response [CR] + partial response + stable disease) was presented at SGO 2018 (late-breaker abst. 4).

Methods

Pts had PSR OC, gBRCA1 or gBRCA2 mutation, and had received at least one prior line of platinum. Pts received olaparib 300 mg PO BID for a 4-wk runin, then olaparib 300 mg PO BID and durvalumab 1.5 g IV q 4 wks until progressive disease. Tumours were assessed by RECIST 1.1 at baseline, 4 wks, then every 8 wks. Primary endpoints were 12wk DCR and safety. Secondary endpoints were 28-wk DCR, objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and biomarker analyses.

Results

Thirty-two/thirty-four pts treated were eligible. With the data cut-off on 1 Nov 2018, 28% pts were still on treatment. Most common ≥Grade 3 AEs were anaemia (17.6%), elevated lipase (11.8%), neutropenia (8.8%), and lymphopenia (8.8%). Five pts discontinued olaparib and three discontinued durvalumab due to an adverse event. The 28-wk DCR was 65.6% (90% CI: 49.6%, 79.4%). ORR was 71.9% (95% CI: 53.25%, 86.25%) with a total of seven CRs. Median PFS was 11.1 months (95% CI: 8.2, 15.9) with a median DoR of 10.2 months (25/75th percentile: 5.6, NC). Second-line pts (N = 13, 40.6%) had not yet reached the medians for PFS or DoR. Median OS for all pts was not yet reached, with 87.0% of pts alive at 24 months (median follow up = 20.4 months). Updated results will be presented.

Conclusions

The combination of olaparib and durvalumab was well tolerated and showed promising median PFS and DoR. Median PFS and DoR for pts with fewer prior lines of chemotherapy was not yet reached, suggesting that these pts may derive a greater benefit from the combination. The CR rate was higher than anticipated. This cohort has been expanded to further explore the durability of this chemotherapy-sparing combination.

Clinical trial identification

NCT02734004.

Editorial acknowledgement

Emma Robinson, Mudskipper Business, Ltd, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

Y. Drew: Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Tesaro ; Advisory / Consultancy: Genmab; Research grant / Funding (institution): Oncology; Research grant / Funding (institution): Veratsem. B. Kaufman: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Medison. S. Banerjee: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. P. Roxburgh: Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro. R.H. Alvarez: Honoraria (self): Eisai; Honoraria (self): Puma; Leadership role: Cancer Treatment Center of America. S. Domchek: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Clovis Oncology; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): PharmaMar. C. Gresty: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H.K. Angell: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. V. Rocher Ros: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. K. Meyer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Lanasa: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Herbolsheimer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.

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Poster Discussion – Gynaecological cancers Poster Discussion session

Invited Discussant 995PD, 996PD, 997PD and 1190PD (ID 6820)

Lecture Time
10:30 - 10:50
Speakers
  • Sven Mahner (Munich, Germany)
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30
Poster Discussion – Gynaecological cancers Poster Discussion session

Q&A led by Discussant (ID 6823)

Lecture Time
10:50 - 11:00
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30
Poster Discussion – Gynaecological cancers Poster Discussion session

LBA63 - Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: Impact on adjuvant therapy (ID 1518)

Presentation Number
LBA63
Lecture Time
11:00 - 11:00
Speakers
  • Carien L. Creutzberg (Leiden, Netherlands)
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30

Abstract

Background

The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) versus radiotherapy alone (RT) for women with stage I-III endometrial cancer with high-risk features (HREC). Since the TCGA defined 4 molecular subgroups of EC with strong prognostic value, we investigated outcomes and impact of chemotherapy for each molecular subgroup using tissue samples from PORTEC-3 trial participants.

Methods

Paraffin-embedded tissues of 423 consenting patients (64% of 660) were collected. Immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE pathogenic exonuclease domain mutations were done to classify tumours as p53 mutant staining (p53abn), POLE ultramutated (POLEmut), MMR deficient (MMRd), or no specific molecular profile (NSMP). The Kaplan-Meier method, log-rank test and Cox model were used for analysis.

Results

Molecular analysis was successful in 410 HREC (97%), identifying the four subgroups; p53abn (n = 92, 22%), POLEmut (n = 52, 13%), MMRd (n = 137, 33%) and NSMP (n = 129, 32%). Five-year recurrence free survival (RFS) was 50% for patients with p53abn HREC, 98% for POLEmut, 74% for MMRd and 76% for NSMP (p < 0.0001). Patients with p53abn HREC significantly benefited from combined chemotherapy and radiotherapy (5-year RFS with CTRT 61% versus 37% for RT, log-rank p = 0.015, Table 1). In contrast, POLEmut-HREC had 97-100% survival in both trial arms, and 5-year RFS for MMRd-HREC was 72 vs 76% for CTRT vs RT.

Recurrence-free survival by molecular subgroup

Events5-year estimate %HR (95% CI)P value of HR
p53abn EC
RT2837,21
CTRT2061,10,50 (0,28-0,88)0,017
POLEmut EC
RT196,61
CTRT01000,02 (<0,01->104)0,632
MMRd EC
RT1775,81
CTRT1872,41,15 (0,59-2,22)0,687
NSMP EC
RT1968,91
CTRT1781,20,71 (0,37-1,37)0,311

Conclusions

Molecular EC classification has a strong prognostic value in HREC and better identifies those who benefit from adjuvant CTRT than clinicopathological factors. Patients with p53abn HREC had significantly improved RFS with adjuvant CTRT, while those with MMRd did not seem to benefit from chemotherapy. Patients with POLEmut HREC had an excellent RFS in both arms. Future trials should incorporate the molecular classification and target specific subgroups.

Clinical trial identification

NCT00411138.

Legal entity responsible for the study

Leiden University Medical Center.

Funding

Koningin Wilhelmina Fonds voor de Nederlandse Kankerbestrijding (KWF).

Disclosure

A. Leary: Travel / Accommodation / Expenses, Officer / Board of Directors: AZ; Officer / Board of Directors: Tesaro; Officer / Board of Directors: Clovis; Officer / Board of Directors: MSD; Officer / Board of Directors: Grisdstone; Officer / Board of Directors: Seattle Genetics; Officer / Board of Directors: Gamamabs; Officer / Board of Directors: Biocad; Travel / Accommodation / Expenses: Roche . H.W. Nijman: Leadership role, Founder: SME Vicinivax; Advisory / Consultancy: Aduro; Advisory / Consultancy: TRON ; Advisory / Consultancy: Merck. All other authors have declared no conflicts of interest.

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Poster Discussion – Gynaecological cancers Poster Discussion session

998PD - Analysis of tumour samples from SOLO1: Frequency of BRCA specific loss of heterozygosity (LOH) and progression-free survival (PFS) according to homologous recombination repair deficiency (HRD)-LOH score (ID 4592)

Presentation Number
998PD
Lecture Time
11:00 - 11:00
Speakers
  • Charlie Gourley (Edinburgh, United Kingdom)
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30

Abstract

Background

In SOLO1 (NCT01844986; GOG-3004), maintenance olaparib significantly improved PFS vs placebo (HR 0.30; 95% CI 0.23–0.41; Moore et al. NEJM 2018) in patients (pts) with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation (BRCAm), who were in clinical complete or partial response after first line treatment, which includes surgery and platinum-based chemotherapy. We analyzed BRCA LOH and PFS by genome-wide HRD-LOH score in SOLO1.

Methods

Archival diagnostic tumour samples from 341/391 pts from SOLO1 were analysed using the Foundation Medicine F1CDx clinical trial assay. Tumour BRCA1 and BRCA2 LOH was determined using the SGZ-computational method (Sun et al. 2018). HRD-LOH score (genomic instability scar) was also generated and compared with PFS using a Cox Proportional Hazards model.

Results

Of evaluable tumours, 99% (275/277) had BRCA1 or BRCA2 LOH, including 2 pts with a somatic BRCAm. Two germline BRCA2m tumours lacked LOH. 283/341 (83.0%) tumours sequenced at FMI were evaluable for HRDLOH score. Using established cut-offs of 14 and 16 (Swisher et al. 2017); 84% (237/283) and 77% (218/283), respectively, would be considered HRD-LOH high. BRCAm pts with HRD-LOH scores <14 or < 16 derived similar benefit with olaparib compared to those with high scores (Table).

Progression-free survival
HRD-LOH score subgroupTreatment armNNumber (%) eventsHR95% CI
HRD-LOH score <14Olaparib Placebo27 199 (33.3) 14 (73.7)0.200.08, 0.45
HRD-LOH score ≥14Olaparib Placebo165 7263 (38.2) 56 (77.8)0.320.22, 0.46
HRD-LOH score <16Olaparib Placebo43 2218 (41.9) 16 (72.7)0.290.15, 0.58
HRD-LOH score ≥16Olaparib Placebo149 6954 (36.2) 54 (78.3)0.290.20, 0.43

Conclusions

As surgery is part of first-line treatment, platinum sensitivity cannot be determined in all pts. However, our results show that in patients with BRCAm tumours, BRCAm LOH is almost universal in ovarian cancer in the first-line setting. The majority of BRCAm tumours also have high HRD-LOH scores at diagnosis, with significant olaparib benefit demonstrated in pts with both high and low HRD-LOH scores. Assessing BRCA LOH and HRD-LOH scores does not discriminate the extent of olaparib benefit in newly diagnosed BRCAm advanced OC.

Clinical trial identification

NCT01844986.

Editorial acknowledgement

Emma Robinson, PhD, from Mudskipper Business Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Legal entity responsible for the study

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Funding

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Disclosure

C. Gourley: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Tesaro; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Nucana; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy: Foundation One; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Sierra Oncology; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Aprea. J.S. Brown: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Z. Lai: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Lao-Sirieix: Shareholder / Stockholder / Stock options, Full / Part-time employment, Spouse / Financial dependant, Spouse full-time employee: AstraZeneca; Licensing / Royalties, Named inventor on patent licensed to Medtronic. Not related to the topic of the abstract: Medtronic. C.E. Elks: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H. McGarvey: Full / Part-time employment: AstraZeneca. T. French: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. T. Milenkova: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Bloomfield: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Rowe: Full / Part-time employment: AstraZeneca. D. Hodgson: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J.C. Barrett: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. K. Moore: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Financial conflict of interest with AstraZeneca for 2018 related to speaking engagements following SOLO-1 and travel: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Honoraria (self): Prime Oncology; Honoraria (self): Research to Practice; Honoraria (self): PER; Advisory / Consultancy: Advaxis; Advisory / Consultancy: Immunogen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy: Oncomed; Advisory / Consultancy: Samumed; Advisory / Consultancy: Aravive; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Eisai; Research grant / Funding (self): Lilly; Research grant / Funding (self): PTC Therapeutics; Research grant / Funding (institution): LEAP, AbbVie, Boehringer Ingelheim, Regeneron. P. DiSilvestro: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro. E.A. Harrington: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca.

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Poster Discussion – Gynaecological cancers Poster Discussion session

999PD - Immune-related gene expression signatures (irGES) in patients (pts) with ovarian clear cell carcinomas (OCCC): A multicenter analysis (ID 4751)

Presentation Number
999PD
Lecture Time
11:00 - 11:00
Speakers
  • Valerie Heong (Singapore, Singapore)
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30

Abstract

Background

We previously showed that OCCC can be classified into 4 molecular subgroups based on their irGES profiles with distinct clinicopathological characteristics and prognostic outcomes. A combined analysis of samples from 3 independent centres was performed to investigate the prognostic relevance of the irGES profiles in a larger cohort of OCCC patients.

Methods

Immune-related gene profiling was performed on 255 FFPE OCCC samples collected from 3 centres (NUH, Singapore, Saitama, Japan, and Edinburgh, UK) using the nanoString nCounter PanCancer Immune Profiling Panel. Unsupervised hierarchical clustering analysis was performed and correlated with clinical outcome. MMR protein levels were assessed by immunohistochemistry.

Results

Total of 255/264 samples from 3 independent cohorts were successfully profiled. Median age at diagnosis was 57 yrs. 137 (53.7%) were stage 1 (Singapore 46.9%, Saitama 65.8%, Edinburgh 50.6%) with 113 (44.3%) Stages 2-4 (Singapore 47.9%, Saitama 34.2%, Edinburgh 49.4%) and 5 (1.9%) missing data. 68.8%, 80.3% and 80.7% of pts from Singapore, Saitama and Edinburgh respectively, received adjuvant treatment. Median PFS for OCCC pts from Singapore, Saitama and Edinburgh were 27, 29.2 and 31.9 mths, respectively. Median OS were 33.5, 35.1 and 41.6 mths respectively for pts from Singapore, Saitama and Edinburgh. Based on irGES, 4 distinct molecular subgroups of OCCCs were consistently identified and reproducible. The PD-1 high subgroup was observed to have poorer 3 yr OS rate (52% vs 57% vs 73% vs 74%, p = 0.05) and a trend towards poorer 3 year PFS rate (42% vs 58.7% vs 51% vs 65%, p = 0.12) compared to the CTLA4, ProA and AP subgroups respectively. A similar trend was observed when pts were stratified based on stage and whether they received adjuvant treatment. MMR expression levels were noted to be deficient in 6.3% and 5.1% of pts from Singapore and Saitama, respectively and were not significantly associated with any irGES group.

Conclusions

Clinical outcomes, based on irGES profiles, appeared to be similar across Asian and Caucasian OCCC pts. 4 molecular subgroups based on their irGES profiles were consistently identified between 3 independent cohorts with distinct prognostic outcomes.

Legal entity responsible for the study

The authors.

Funding

NUHS Clinician Scientist Programme-Residency (NCSP-R) Grant NMRC -Centre grant scheme Yong Siew Yoon fellowship grant Clinician Scientist Award (IMAC) CSA-NMRC grant Nicola Murray Foundation.

Disclosure

C. Gourley: Honoraria (self), Advisory / Consultancy: Roche, AstraZeneca, Tesaro, Nucana, Clovis, Foundation One, Sierra Oncology, Cor2Ed; Research grant / Funding (self): AstraZeneca, Novartis, Aprea, Nucana, Tesaro; Licensing / Royalties: PCT/US2012/040805, PCT/GB2013/053202, 1409479.1, 1409476.7 and 1409478.3. D.S. Tan: Honoraria (self): Roche, Bayer, MSD, Genmab, AstraZeneca, Merck Serono, Tessa Therapeutics, Novartis; Research grant / Funding (institution): Bayer, Karyopharm, AstraZeneca. R. Huang: Spouse / Financial dependant: ACT genomics Singapore. All other authors have declared no conflicts of interest.

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Poster Discussion – Gynaecological cancers Poster Discussion session

Invited Discussant LBA63, 998PD and 999PD (ID 6821)

Lecture Time
11:00 - 11:20
Speakers
  • Robert L. Coleman (Houston, TX, United States of America)
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30
Poster Discussion – Gynaecological cancers Poster Discussion session

Q&A led by Discussant (ID 6824)

Lecture Time
11:20 - 11:30
Location
Valencia Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
10:30 - 11:30