SABCS 2022 Takeaways - 8
8
CLINICAL
TRIALS
UPDATES
A
*
DESTINY-Breast02 (GS2-01)
Key findings presented by Ian
Krop, MD, PhD:
* Trastuzumab deruxtecan (T-DXd)
significantly improved median progression-free
survival compared
with physician's choice-therapy
(17.8 months vs. 6.9 months)
* Median overall survival also was
improved (see slide)
* Duration of response was more
than double with T-DXd (19.6 months vs. 8.3 months)
DESTINY-Breast02
San Antonio Breast Cancer Symposium® - December 6-10, 2022
Key Secondary Endpoint: OS
100
T-DXd: 89.4% (95% CI, 85.9-92.1)
TPC: 74.7% (95% CI, 67.4-80.4)
80
T-DXd: 65.9% (95% CI, 60.7-70.7)
TPC: 54.3% (95% CI, 46.3-61.6)
60
40
20
+
Censor
T-DXd (n = 406)
TPC (n = 202)
Patients still at risk
TPC (202) 202 192 187 182 178 173 167 161 157 151 142 136 130 124 118 114 111 110 106 95 89 79 76 72 61 53 50 46 38 33 29 28 25 22 22 18 15 13 12 7 6 5 4 3 1 1 0
Time, months
T-DXd (406) 406 404 400 390 385 382 374 366 357 352 350 346 339 331 317 306 295 282 277 257 234 215 196 183 160 144 139 122 104 93 82 72 63 51 40 34 29 25 19 10 8 6 3 1 1 1 0
In the TPC arm
* 69.3% (140/202) of patients received a new systemic anticancer treatment
* 25.7% (52/202) of patients received T-DXd in the post-trial setting
aThe boundary for statistical significance is 0.0040. HR, hazard ratio; mo, month; NE, not estimable; OS, overall survival; T-DXd, trastuzumab deruxtecan; TPC, treatment of physician's choice.
This presentation is the intellectual property of the author/presenter. Contact them at Ian.krop@yale.edu for permission to reprint and/or distribute.
* Grade 5 interstitial lung disease (ILD) was 0.5% which
is lower than previous DESTINY-Breast01 (2.7%)
* Confirms favorable risk-benefit profile of T-DXd for
patients with advanced HER2+ breast cancer as found
in DESTINY-Breast01
HR (95% CI): 0.6575 (0.5023-0.8605)
26.5 (21.0-NE)
Median (95% CI), months
39.2 (32.7-NE)
T-DXd
P =0.0021a
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46
TPC
» At first data cutoff:
* Of the response-evaluable population: overall response
rate was 68% (15 partial responses and 2 complete
response) with no endocrine therapy vs. 58% (12
partial and 2 complete responses) for T-DXd plus
endocrine therapy
* Residual cancer burden (RCB) 0/1 rate: 15% (both
arms), but data not mature-surgical outcomes
pending (24% in arm A; 31% in Arm B)
* Dynamic changes in HER2 tissue expression noted
after treatment with T-DXd
* Nausea was the most common adverse event (AE); 1
case of grade 2 pneumonitis; dose reductions due to
AEs: 5%
2022 SABCS TAKEAWAYS EDITION
number of trials were presented at SABCS 2022
that informed daily clinical practice and provided
new foundations for further research. Only a few
of those trials are mentioned here so be sure to read the
SABCS Meeting News for detailed coverage.
Improving the Odds with T-DXd
Trastuzumab is a monoclonal
antibody that blocks
HER2 growth signals. The
combination of trastuzumab
and deruxtecan (T-DXd), a
topoisomerase inhibitor, kills
the cancer cell a different way-
by attaching trastuzumab to
a payload of chemotherapy,
which is delivered directly to
the tumor.
Trastuzumab deruxtecan (T-DXd)
basics:
* HER2-directed antibody-drug
conjugate
* Potent topoisomerase I
inhibitor payload
* High drug:antibody ratio of
approximately 8
Stable and tumor-selective linker
* Payload is membrane
permeable so exhibits
bystander antitumor effect
* Accelerated approval in
2019 by U.S. Food and Drug
Administration based on
DESTINY-Breast01 (third-line
therapy for unresectable or
metastatic HER2+ breast
cancer) objective response
data, no comparator
* Later receives full approval in
second-line setting based on
DESTINY-Breast03 results
TRIO-US B-12 TALENT (GS2-03)
Would the addition of endocrine
therapy improve the efficacy of T-DXd
for patients with HR+/HER2-low
breast cancer?
According to the study presenter,
Aditya Bardia, MD, MPH, this trial
" is the first report of neoadjuvant
T-DXd for patients with hormone
receptor-positive, HER2-low, localized
breast cancer. It could provide
the groundwork for future studies with antibody-drug
conjugates, including T-DXd, for patients with early-stage
breast cancer. "
» 58 patients assigned to T-DXd + anastrozole or to
T-DXd-alone (29 each)
Overall Survival Probability, %
https://www.sabcs.org/
https://www.sabcsmeetingnews.org/
SABCS 2022 Takeaways
Table of Contents for the Digital Edition of SABCS 2022 Takeaways
SABCS 2022 Takeaways - A
SABCS 2022 Takeaways - 1
SABCS 2022 Takeaways - 2
SABCS 2022 Takeaways - 3
SABCS 2022 Takeaways - 4
SABCS 2022 Takeaways - 5
SABCS 2022 Takeaways - 6
SABCS 2022 Takeaways - 7
SABCS 2022 Takeaways - 8
SABCS 2022 Takeaways - 9
SABCS 2022 Takeaways - 10
SABCS 2022 Takeaways - 11
SABCS 2022 Takeaways - 12
SABCS 2022 Takeaways - 13
SABCS 2022 Takeaways - 14
SABCS 2022 Takeaways - 15
SABCS 2022 Takeaways - 16
SABCS 2022 Takeaways - 17
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