Rilvegostomig Plus Trastuzumab Deruxtecan Shows Activity in Early Breast Cancer

In the phase 2 I-SPY2.2 trial, 105 patients with high-risk, ERBB2-negative early breast cancer received neoadjuvant rilvegostomig plus trastuzumab deruxtecan. The modeled pathologic complete response rate was 54% in immune-positive tumors; interstitial lung disease occurred in 12.4%.

Modeled pCR was 54% in immune-positive tumors.
Overall pCR rates were similar to control regimens.
ILD occurred in 12.4% of RT-DXd-treated patients.
Findings are phase 2 and require further evaluation.

I-SPY2.2 was a multicenter, adaptively randomized phase 2 neoadjuvant trial at 30 US sites. It enrolled patients with high-risk stage II/III ERBB2-negative early breast cancer, including ERBB2-low or ultralow tumors. The study evaluated rilvegostomig plus trastuzumab deruxtecan (RT-DXd) as the initial treatment block, with subsequent taxane-based therapy and doxorubicin-cyclophosphamide available according to response and tumor subtype. The primary endpoint was pathologic complete response (pCR). The intention-to-treat population included 105 patients assigned to RT-DXd and 77 to contemporary control regimens.

Among RT-DXd-treated patients, the modeled pCR rate was 54% in immune-positive tumors, meeting the trial’s predefined success threshold. Rates were 57% in hormone receptor-positive and 52% in hormone receptor-negative immune-positive disease. Across treatment blocks, overall pCR rates were similar to control. Among immune-positive patients who achieved pCR, 21 (62%) did so after block A, and 33 (97%) avoided anthracycline-based chemotherapy.

Interstitial lung disease (ILD) occurred in 13 of 105 patients (12.4%), including one grade 3 event; three patients (2.9%) had serious ILD. Enrollment was paused twice for review of grade 2 or higher ILD and resumed after data safety monitoring board approval. These phase 2 findings support further evaluation in biomarker-selected patients but do not establish RT-DXd as a replacement for standard neoadjuvant treatment. The source reports serial chest CT monitoring; full-text details were unavailable.

In practice

For patients with high-risk stage II/III ERBB2-negative early breast cancer, this phase 2 trial found a modeled pCR rate of 54% with initial rilvegostomig plus trastuzumab deruxtecan in immune-positive tumors. Some immune-positive patients who achieved pCR avoided anthracycline-based chemotherapy, but overall pCR rates across treatment blocks were similar to control regimens. ILD occurred in 12.4%, including one grade 3 event, and enrollment was paused twice for safety review. These findings are promising but do not establish this regimen as a standard alternative; further evaluation is needed.

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Source

JAMA Oncology: Rilvegostomig Plus Trastuzumab-Deruxtecan for Early-Stage Breast Cancer ↗

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