Key takeaways:
- Second-line trastuzumab deruxtecan-nxki considerably improved outcomes for superior gastric cancers in contrast with paclitaxel plus ramucirumab.
- Affirmation of HER2 standing after first-line remedy is vital.
CHICAGO — Second-line trastuzumab deruxtecan-nxki considerably prolonged OS in contrast with paclitaxel plus ramucirumab for sufferers with superior gastric cancers beforehand handled with trastuzumab, in response to randomized section 3 trial outcomes.
The findings, introduced at ASCO Annual Assembly, highlighted the significance of getting a secondary biopsy following first-line remedy to guage HER2 standing, lead creator Kohei Shitara, MD, director of the division of gastrointestinal oncology at Nationwide Most cancers Middle Hospital East in Kashiwa, Japan, stated throughout a press briefing.
Knowledge derived from Shitara Ok, et al. Summary LBA4002. Introduced at: ASCO Annual Assembly; Could 30-June 3, 2024; Chicago.
Kohei Shitara
“Our trial means that [trastuzumab deruxtecan-nxki (T-DXd)] is the most effective second-line remedy for sufferers who’ve remaining HER2 positivity after trastuzumab,” he stated.
Head-to-head comparability
Between 5% and 17% of sufferers with gastric cancers are HER2-positive, in response to research background.
First-line remedy contains trastuzumab (Herceptin, Genentech) plus chemotherapy. Some sufferers additionally obtain pembrolizumab (Keytruda, Merck).
Nevertheless, “most sufferers expertise illness development,” Shitara stated.
Each trastuzumab deruxtecan-nxki (Enhertu; AstraZeneca, Daiichi Sankyo) and paclitaxel plus ramucirumab (Cyramza, Eli Lilly & Co.) have been permitted as second-line therapies.
Shitara and colleagues evaluated the therapies head-to-head within the DESTINY-Gastric04 trial.
Researchers randomly assigned 494 sufferers with metastatic or unresectable HER2-positive gastric most cancers or gastroesophageal junction adenocarcinoma to obtain both 6.4 mg T-DXd (n = 246) each 3 weeks or paclitaxel plus ramucirumab (n = 248).
Individuals needed to have a latest biopsy to substantiate HER2 standing. As much as 50% of sufferers lose HER2 standing after first-line trastuzumab, Shitara stated.
Individuals additionally couldn’t have energetic central nervous system metastases.
OS served as the first endpoint. PFS, confirmed goal response charge, length of response and security served as secondary endpoints.
‘Lengthy-term profit’
Sufferers who obtained T-DXd had a considerably longer OS than these handled with paclitaxel plus ramucirumab (median, 14.7 months vs. 11.4 months; HR = 0.7; 95% CI, 0.55-0.9).
The T-DXd arm had superior OS charges at 12 months (57.6% vs. 48.9%) and 24 months (29% vs. 13.9%).
This instructed “long-term profit,” Shitara stated.
Sufferers who obtained T-DXd additionally had considerably improved PFS (median, 6.7 months vs. 5.6 months; HR = 0.74; 95% CI, 0.59-0.92) and ORR (44.3% vs. 29.1%; P = .0006).
The T-DXd arm had an extended length of response (median, 7.4 months vs. 5.3 months) and higher illness management charge (91.9% vs. 75.9%), as effectively.
Sufferers who obtained T-DXd had decrease charges of grade 3 or worse treatment-emergent antagonistic occasions (68% vs. 73.8%), severe treatment-emergent antagonistic occasions (41% vs. 43.3%) and occasions related to dose discontinuation (14.3% vs. 17.2%), dose interruption (56.1% vs. 60.5%), dose discount (31.6% vs. 37.3%) and dying (9% vs. 15%).
Interstitial lung illness and pneumonitis occurred extra regularly within the T-DXd arm (13.9% vs. 1.3%), however just one participant had a grade 3 occasion and none had grade 4 or 5 occasions.
“Outcomes assist additional analysis of T-DXd in an earlier-line setting,” Shitara stated.
ASCO knowledgeable Pamela L. Kunz, MD, PhD, professor of inner drugs and director of the Middle for Gastrointestinal Cancers at Smilow Most cancers Hospital and Yale Most cancers Middle, described the outcomes as “observe validating” within the U.S. and different international locations the place T-DXd is permitted as second-line remedy, and “observe altering” the place it isn’t.
She famous limitations although, together with the elevated charge of pneumonitis, which may enhance the necessity to display screen for sufferers with underlying lung circumstances.
Kunz additionally mentioned the associated fee and availability of re-biopsy, however highlighted its significance.
“Precision drugs is just exact if we really get up-to-date info as mutations can change over time,” she stated.
Sources/Disclosures
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Shitara Ok, et al. Summary LBA4002. Introduced at: ASCO Annual Assembly; Could 30-June 3, 2024; Chicago.
Disclosures:
Daiichi Sankyo sponsored the research. AstraZeneca entered into a worldwide improvement and commercialization collaboration settlement with Daiichi Sankyo for trastuzumab deruxtecan-nxki.
