Found 2 Presentations For Request "356P"

Poster Display session 2 Poster Display session

356P - Use of trastuzumab emtansine (T-DM1; K) after pertuzumab + trastuzumab (PH) in patients with HER2-positive metastatic breast cancer (mBC): Challenges in assessing effectiveness of treatment sequencing in the real world (RW) (ID 4540)

Presentation Number
356P
Lecture Time
12:00 - 12:00
Speakers
  • Thibaut Sanglier (Basel, Switzerland)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Introduction of PH (2012) and K (2013) in the US changed the standard-of-care for HER2-positive mBC. RW studies reported decreased K effectiveness in pts with PH pre-tx. We studied whether timing of PH and K availability in clinical practice could introduce selection bias (i.e. pts with K after PH in early yrs of availability may have to have had rapid progression during PH tx to be included in RW analyses).

Methods

Using de-identified data from the US-based Flatiron electronic health record-derived database, we selected pts diagnosed with mBC on/after 1 Jan 2011 and initiating K between 1 Feb 2013 and 31 Jul 2018. Primary analysis included all pts receiving K (any tx line). Subgroup analysis focused on pts with 2nd-line K tx after PH tx. Time from index date to next tx/death (TTNT) was used as a proxy for progression-free survival.

Results

Primary cohort (N = 533) demographics were generally consistent across yrs (2013–18); median age was 61 yrs; 89% had prior HER2-targeted tx; 23% had brain metastases (mets); 68% had visceral mets. In pts with (n = 231) vs without (n = 79) prior PH, median age was 61 vs 65 yrs, mean time from mBC diagnosis was 16 vs 18 months, 27% vs 20% had brain mets, 74% vs 58% had visceral mets. Additional findings are shown (Table). Prevalence of prior PH exposure almost doubled over the yrs. In 2nd-line K treated pts with prior PH, time from mBC to K increased over the yrs, paralleled by a numerical increase in median TTNT.

356P

201320142015201620172018
Primary cohort (N = 533)
 N517710810611774
 Prior PH, n (%)18 (35.3%)35 (45.5%)72 (66.7%)80 (75.5%)77 (65.8%)53 (71.6%)
 TTNT, median months (95% CI)6.8 (4.9–14.2)6.5 (4.2–9.2)7.6 (4.7–9.8)6.3 (5.1–8.4)8.4 (6.4–10.3)Data not yet mature
 % Censored13.7%10.4%9.3%17.0%36.8%
Subgroup analysis (N = 231)
 Pts with 2nd-line K use after PH, N132556515234
 mBC to K initiation in pts with 2nd-line K use after PH, mean months (SD)12.7 (6.9)13.1 (8.5)13.0 (8.0)16.0 (12.9)17.9 (12.5)18.6 (11.6)
 TTNT in pts with 2nd-line K use after PH, median months (95% CI)5.1 (3.0–7.5)7.2 (4.6–11.7)6.6 (4.5–8.4)10.3 (5.6–12.8)Data not yet mature
 % Censored7.9%8.9%15.7%40.4%

CI, confidence internal; SD, standard deviation.

Conclusions

Prevalence of PH pre-tx increased, yet K effectiveness remained consistent across yrs. With PH launched shortly before K, the initial pts receiving K were possibly selected due to shorter benefit from prior PH. This selection bias may explain reports of lower K effectiveness in pts with prior PH tx. This illustrates the challenges of assessing tx sequence effectiveness shortly after tx approval.

Editorial acknowledgement

Writing assistance was provided by Meredith Kalish, MD, of Ashfield Healthcare Communications (a UDG Healthcare plc company), and funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

T. Sanglier: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. C. Flores: Full / Part-time employment: Genesis Research. E. Flahavan: Shareholder / Stockholder / Stock options: Eli Lilly; Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. N. Lindegger: Honoraria (self), Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche; Shareholder / Stockholder / Stock options: Novartis; Shareholder / Stockholder / Stock options: Idorsia; Shareholder / Stockholder / Stock options: J&J. F. Montemurro: Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Ely Lilly; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.

Collapse
Poster Display session 3 Poster Display session

1356P - Increase in S100B and LDH as early outcome predictors for non-responsiveness to anti-PD-1 monotherapy in advanced melanoma (ID 3120)

Presentation Number
1356P
Lecture Time
12:00 - 12:00
Speakers
  • Elisa A. Rozeman (Amsterdam, Netherlands)
Session Name
Poster Display session 3
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
30.09.2019
Time
12:00 - 13:00

Abstract

Background

Immune-checkpoint inhibitors have revolutionized advanced melanoma care. Despite major improvements in survival, many patients do not derive long-term benefit and treatment could cause severe side-effects. Since several new (combination) therapies are or will become available, early prediction of non-responsiveness (NR) to anti-PD-1 monotherapy becomes relevant in order to enable early switch to next line (combination) treatment and avoid nonsensical care.

Methods

Advanced melanoma patients treated with pembrolizumab (PEM) who started PEM between June 2014 and August 2016 were included in this retrospective analysis. S100 and lactate dehydrogenase (LDH) levels were routinely determined prior to initiation of PEM and every 3-weeks during treatment. NR to treatment was defined as progressive disease or death at 6 months after start of PEM. Biomarker response characteristic (BReC) plots were obtained and LDH and S100 response cut-offs were determined based on two criteria: specificity for NR > 95% and feasibility to use in clinical practice. Next, sensitivity, specificity and predictive values were generated per follow-up time point (week 3, 6, 9, 12 and 15).

Results

166 advanced melanoma patients were included. The BReC analyses showed clear relations between an early (week 3 to 15) increase in tumor biomarker and NR. An increase of > 50% in LDH or a > 100% increase in S100 above the upper limit of normal compared to baseline at any follow-up interval was determined as criterion to positively test for NR. Obtained specificity ranged from 0.97-0.98 and the positive predictive value ranged from 0.92-0.96 for the studied follow-up intervals. Obtained sensitivity for detecting non-responsiveness ranged from 0.25 (95% CI; 0.16-0.35) at 3 weeks of follow-up to 0.35 (95% CI; 0.24-0.47) at 12 weeks of follow-up.

Conclusions

An early increase in S100 and/or LDH are strong parameters for non-responsiveness to PD-1 blockade in advanced melanoma. Prospective confirmation is needed before clinical implementation.

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Netherlands Cancer Institute.

Disclosure

E.A. Rozeman: Travel / Accommodation / Expenses: NanoString; Travel / Accommodation / Expenses: MSD. J.V. van Thienen: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. J.B.A.G. Haanen: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AZ/MedImmune; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Immunocore; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Neon Therapeutics; Advisory / Consultancy: Celsius; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Gadet. C.U. Blank: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Lilly ; Advisory / Consultancy: GSK; Advisory / Consultancy: GenMab; Research grant / Funding (institution): NanoString; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.

Collapse