The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Third-line treatment of HER2-positive, metastatic colorectal cancer (CRC) with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) demonstrated promising efficacy, according to results from a phase 2 trial presented at the ASCO20 Virtual Scientific Program.

“These data demonstrate the potential of T-DXd as a treatment option for patients with advanced HER2-positive CRC,” Salvatore Siena, MD, of Università degli Studi di Milano in Italy, and lead author and presenter of the study, said.

T-DXd contains an anti-HER2 antibody that is linked to deruxtecan, a topoisomerase I inhibitor. T-DXd has demonstrated promising results in early studies of advanced HER2-positive solid tumors. The purpose of this trial was to determine the safety and efficacy of T-DXd among patients with HER2-positive, metastatic CRC, specifically.

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The multicenter, open-label, phase 2 DESTINY-CRC01 trial treated 78 patients with T-DXd who had HER2-positive, RAS wild-type, unresectable or metastatic CRC and had progressed on 2 or more prior regimens. Patients were divided into 3 cohorts: cohort A included patients with HER2 immunohistochemistry (IHC) of 3+ or IHC 2+/in situ hybridization (ISH)–positive; cohort B included patients with HER2 IHC 2+/ISH-negative; and cohort C included patients with HER2 IHC 1+.

The primary endpoint was objective response rate (ORR) in cohort A. Secondary endpoints included ORR in cohorts B and C, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

At baseline in cohort A, the median age was 57 years and 52.8% of patients were female. Left colon or rectum cancer was present in 88.7% of patients, and the median number of prior lines of therapy among all enrolled patients was 4 (range, 2-11).

Among the 53 patients in cohort A, the ORR was 45.3% (95% CI, 31.6%-59.6%), which included 1.9% of patients who achieved complete response, 43.4% who experienced a partial response, and 37.7% who achieved stable disease. The median DOR was not yet reached.

None of the patients in cohorts B or C responded to T-DXd. That meant that in sum across chohorts, at a follow-up of August 2019, only 30 of 78 patients (38.5%) remained on treatment. Of the 61.5% of individuals who discontinued treatment, 41% experienced progressive disease and 9% saw clinical progression.

The ORR was similar among patients who had received prior anti-HER2 therapy, at 43.8%.

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The median PFS was 6.9 months (95% CI, 4.1 months-not evaluable). The median OS was not yet reached.

Among all enrolled patients, 61.5% experienced grade 3 or higher treatment-emergent adverse events (TEAEs), with the most common including nausea, neutropenia, and anemia.

Of special interest, treatment-related interstitial lung disease (ILD) occurred in 6.4% of patients, including 2.6% who developed grade 5 ILD. Treatment discontinuation due to TEAEs occurred in 9% of patients. Dr Siena acknowledged that ILD is “an important risk and requires careful monitoring and prompt intervention.”

These data “demonstrated promising and durable activity in patients with HER2-positive metastatic CRC refractory to standard therapies,” Dr Siena said.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.


Siena S, Di Bartolomeo M, Raghav KPS, et al. A phase II, multicenter, open-label study of trastuzumab deruxtecan (TDXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 4000.