HER2-targeted therapy shows antitumor activity in metastatic colorectal cancer
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Trastuzumab deruxtecan demonstrated durable benefit among patients with HER2-expressing metastatic colorectal cancer, according to findings of the phase 2 DESTINY-CRC01 study presented during the ASCO20 Virtual Scientific Program.
Interstitial lung disease appeared to be an important risk that requires careful recognition and intervention, researchers noted.
“Trastuzumab deruxtecan [Enhertu; AstraZeneca, Daiichi Sankyo] is a novel antibody-drug conjugate composed of three components — an anti-HER2 immunoglobin G1 monoclonal antibody, a tetrapeptide-based cleavable linker, and a topoisomerase I inhibitor payload. Early studies have shown promising activity in advanced HER2-expressing tumors,” Salvatore Siena, MD, professor of medical oncology at Università degli Studi di Milano and director of Niguarda Cancer Center at Grande Ospedale Metropolitano Niguarda in Italy, said during a presentation.
The open-label, multicenter DESTINY-CRC01 trial included 78 patients (median age, 58.5 years; range, 27-79; 52.6% men) with HER2-expressing RAS wild-type metastatic colorectal cancer (89.7% left colon or rectum cancer). All patients received at least two prior lines of treatment (median prior lines, 4; range, 2-11), and 20.5% had prior anti-HER2 therapy. Researchers excluded patients who had a prior history of or current/suspected interstitial lung disease.
The study consisted of three cohorts. Cohort A included 53 patients with immunohistochemical 3-positive or immunohistochemical 2-positive/in situ hybridization-positive disease; cohort B included seven patients with immunohistochemical 2-positive/ in situ hybridization-negative disease; and cohort C included 18 patients with immunohistochemical 1-positive disease.
All patients received 6.4 mg/kg trastuzumab deruxtecan IV every 3 weeks.
Confirmed objective response rate in cohort A served as the primary endpoint. Disease control rate, duration of response, PFS, OS and ORR in cohorts B and C served as secondary endpoints.
Median treatment duration was 3.5 months (95% CI, 2.1-4.3) overall and 4.8 months (95% CI, 3.9-5.8) in cohort A, with 38.5% of patients remaining on study treatment (41% discontinued due to disease progression and 9% due to clinical progression).
Results showed a confirmed ORR in cohort A of 45.3% (95% CI, 31.6-59.6). This included one complete response and 23 partial responses. Twenty patients achieved stable disease, for a disease control rate of 83% (95% CI, 70.2-91.9).
Median duration of response was not reached.
Researchers observed no responses in cohorts B or C.
Among those who received prior anti-HER2 therapy, researchers observed an ORR of 43.8% (95% CI, 19.8-70.1).
Median PFS was 6.9 months (95% CI, 4.1 to not reached) and median OS was not reached.
Grade 3 or higher treatment-emergent adverse events occurred among 61.5% of patients. These included decreased neutrophil count (21.8%) and anemia (14.1%). Interstitial lung disease associated with study treatment was confirmed in 6.4% of patients.
Seven patients discontinued treatment as a result of treatment-related adverse events.
“We observed a safety profile consistent with what has been previously reported,” Siena said during the presentation. “These data demonstrate the potential of trastuzumab deruxtecan as a treatment option for patients with advanced HER2-positive metastatic colorectal cancer.” – by Jennifer Southall
Reference:
Siena S, et al. Abstract 4000. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
Disclosures: Daiichi Sankyo Co. Ltd. funded this study. Siena reports consultant/advisory roles with Amgen, Bayer, Bristol-Myers Squibb, CheckmAb, Clovis Oncology, Daiichi Sankyo, Incyte, Merck, Novartis, Roche/Genentech and Seattle Genetics; research funding from MSD Oncology; stock and other ownership interests in Guardant Health and Myriad Genetics; travel, accommodations or expenses from Amgen, Bayer and Roche; and patents, royalties and other intellectual property from Amgen. Please see the abstract for all other researchers’ relevant financial disclosures.
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Siena S, et al. Abstract 4000. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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