Second-line Enhertu improved key survival finish factors versus Cyramza plus paclitaxel for HER2+ gastric most cancers or gastroesophageal junction adenocarcinoma: © inventory.adobe.com.
Amongst sufferers with HER2-positive unresectable or metastatic gastric most cancers or gastroesophageal junction adenocarcinoma (GC/GEJ), second-line therapy with Enhertu (fam-trastuzumab deruxtecan-nxki) had a clinically significant and statistically important profit in comparison with Cyramza (ramucirumab) plus paclitaxel. The investigative mixture particularly improved general survival charges amongst sufferers.
These findings had been generated by the part 3 DESTINY-Gastric04 trial, information from which was concurrently shared throughout a press briefing in the course of the 2025 ASCO Annual Assembly, in addition to revealed in The New England Journal of Drugs.
At a median follow-up of 16.8 months for Enhertu and 14.4 months for Cyramza plus paclitaxel, the median general survival was 14.7 months versus 11.4 months , respectively, with a 30% discount in danger of demise. The 6-month general survival charges had been 83.5% versus 74.4%, respectively, the 12-month general survival charges had been 57.6% versus 48.9%, and the 24-month general survival charges had been 29.0% versus 13.9%.
The median progression-free survival with Enhertu was 6.7 months (95% CI, 5.6-7.1) versus 5.6 months with Cyramza plus paclitaxel. The six-month progression-free survival price was 52.6% versus 41.5%, respectively, and the 12-month progression-free survival price was 22.9% versus 13.6%.
The confirmed general response price was 44.3% in all sufferers who acquired Enhertu and 29.1% in all sufferers who acquired Cyramza plus paclitaxel; the distinction was 15.1%. The length of response was 7.4 months versus 5.3 months, respectively. At six months, the length of response price was 58.4% versus 35.7%, respectively, and at 12 months, it was 29.7% versus 15.0%.
The illness management price was 91.9% with Enhertu; 3.0% of sufferers (seven sufferers) achieved a whole response, 41.3% (97 sufferers) achieved a partial response, 47.7% (112 sufferers) achieved steady illness, 5.5% (13 sufferers) had progressive illness, and a pair of.6% (six sufferers) weren’t evaluable. In sufferers who acquired Cyramza plus paclitaxel, the illness management price was 75.9%; 1.3% of sufferers (three sufferers) achieved a whole response, 27.8% (66 sufferers) achieved a partial response, 46.8% (111 sufferers) achieved steady illness, 9.3% (22 sufferers) had progressive illness and 14.8% (35 sufferers) weren’t evaluable.
“Enhertu demonstrated a statistically important and clinically significant enchancment in general survival in contrast with [Cyramza plus paclitaxel] in sufferers with HER2-positive metastatic GC/GEJ within the second line setting,” acknowledged presenting examine writer Dr. Kohei Shitara, director of the Division of Gastrointestinal Oncology on the Nationwide Most cancers Middle Hospital East in Kashiwa, Japan, within the presentation. “DESTINY-Gastric04 confirmed Enhertu as the worldwide [second line] standard-of-care remedy for sufferers with HER2-positive metastatic GC/GEJ.”
Glossary
General survival (OS): the size of time from both the date of prognosis or the beginning of therapy for a illness that sufferers identified are alive.
Development-free survival (PFS): the size of time throughout and after the therapy {that a} affected person lives with the illness however it doesn’t worsen.
General response price (ORR): the proportion of sufferers who’ve a partial or full response to remedy.
DESTINY-Gastric04 was a worldwide, multicenter trial that randomly assigned roughly 494 sufferers to obtain both 6.4 milligrams per kilogram (mg/kg) of intravenous Enhertu as soon as each three weeks (246 sufferers) or intravenous Cyramza at 8 mg/kg on days one and 15 of every 28-day cycle and paclitaxel at 80 mg/m2 on days one, eight and 15 of every 28-day cycle (248 sufferers).
Eligible sufferers had HER2-positive GC/GEJ with HER2 standing confirmed regionally or centrally on a biopsy obtained after development on Herceptin (trastuzumab). Sufferers additionally had no clinically energetic central nervous system metastases.
Exclusion standards included a historical past of noninfectious interstitial lung illness or pneumonitis that was handled with glucocorticoids, energetic interstitial lung illness or pneumonitis, or suspected of getting interstitial lung illness or pneumonitis that might not be dominated out by imaging.
The trial’s main finish level was OS. Key secondary finish factors included progression-free survival per investigator evaluation, confirmed general response price per investigator evaluation, length of response per investigator evaluation and security.
Drug-related treatment-emergent negative effects of any grade affected 93.0% (227 of 244 sufferers) of sufferers who acquired Enhertu and 91.4% (213 of 233 sufferers) of sufferers who acquired Cyramza plus paclitaxel; drug-related treatment-emergent negative effects of grade 3 or increased affected 50.0% and 54.1% of sufferers. The most typical drug-related negative effects that had been grade 3 or increased for Enhertu was neutropenia (28.7%), anemia (13.7%) and leukopenia (12.4%) ramucirumab.
It was additionally famous that interstitial lung illness/pneumonitis occurred in 13.9% of sufferers who acquired Enhertu and 1.3% who acquired Cyramza plus paclitaxel.
Drug-related treatment-emergent negative effects had been related to dose discontinuation, dose interruption, dose discount, and demise, respectively, in 11.5%, 38.5%, 31.1%, and 1.6% of sufferers who acquired Enhertu, and in 13.3%, 51.1%, 36.1%, and 0.9%, respectively, of sufferers who acquired Cyramza plus paclitaxel.
“These outcomes warrant additional analysis of Enhertu within the context of first-line remedy,” wrote the authors of the examine within the paper.
References
- Shitara Okay, Gumus M, Pietrantonio F, et al. Trastuzumab deruxtecan (T-DXd) vs ramucirumab (RAM) + paclitaxel (PTX) in second-line therapy of sufferers (pts) with human epidermal development issue receptor 2-positive (HER2+) unresectable/metastatic gastric most cancers (GC) or gastroesophageal junction adenocarcinoma (GEJA): Main evaluation of the randomized, part 3 DESTINY-Gastric04 examine. Offered at: 2025 American Society of Scientific Oncology Annual Assembly; Could 30-June 3, 2025. Chicago, IL. Summary 4002.
- Shitara Okay, Van Cutsem E, Gümüş M, et al. Trastuzumab deruxtecan or ramucirumab plus paclitaxel in gastric most cancers. N Engl J Med. Revealed on-line Could 31, 2025. doi:10.1056/NEJMoa2503119
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