The completed phase II TOUCH trial evaluated whether palbociclib combined with letrozole and dual HER2 blockade (trastuzumab plus pertuzumab) could replace paclitaxel-based chemotherapy in the neoadjuvant setting for postmenopausal women with HR+/HER2+ early breast cancer. The randomized, open-label, multicentre design aimed to determine whether a chemotherapy-sparing regimen could achieve comparable efficacy.
The TOUCH trial (NCT03644186), a phase II open-label, multicentre, randomized study sponsored by the ETOP IBCSG Partners Foundation, has completed enrollment and intervention. The trial addressed a clinically meaningful question: whether neoadjuvant palbociclib—a CDK4/6 inhibitor—combined with letrozole and dual HER2-targeted blockade using trastuzumab and pertuzumab can serve as a viable alternative to paclitaxel plus trastuzumab and pertuzumab in postmenopausal women with hormone receptor-positive, HER2-positive early breast cancer.
The rationale for this approach stems from the biologically distinct nature of HR+/HER2+ tumors, which co-express estrogen receptor signaling alongside HER2 amplification. CDK4/6 inhibition with palbociclib has demonstrated activity in HR+ metastatic disease, and its combination with endocrine therapy and HER2 blockade represents a mechanistically coherent strategy to suppress both proliferative pathways without cytotoxic chemotherapy. The experimental arm omits conventional chemotherapy entirely, substituting palbociclib and letrozole alongside the established pertuzumab-trastuzumab backbone.
For postmenopausal patients who may have greater sensitivity to chemotherapy-associated toxicities—including peripheral neuropathy from taxane exposure—a chemotherapy-free neoadjuvant regimen would represent a meaningful advance in tolerability and quality of life if non-inferiority or comparable pathologic response rates are confirmed. Full efficacy and safety results from the TOUCH trial have not yet been reported in the available source data, and clinical conclusions await formal publication.
Key points
- Phase II TOUCH trial randomized postmenopausal HR+/HER2+ early breast cancer patients to palbociclib + letrozole + trastuzumab/pertuzumab versus paclitaxel + trastuzumab/pertuzumab in the neoadjuvant setting.
- The experimental arm is entirely chemotherapy-free, relying on CDK4/6 inhibition combined with endocrine therapy and dual HER2 blockade.
- Trial was conducted as an open-label, multicentre, randomized phase II study under the ETOP IBCSG Partners Foundation.
- The study has completed; however, efficacy and safety outcome data are not yet available from the current source.
- If successful, this strategy could reduce chemotherapy exposure in a population where taxane-related toxicity is a significant clinical concern.
Why it matters
HR+/HER2+ early breast cancer represents a subgroup where endocrine and HER2-targeted mechanisms overlap, creating a rationale for chemotherapy-free neoadjuvant regimens. Confirmation of adequate pathologic response with palbociclib-based therapy could meaningfully shift neoadjuvant practice and reduce toxicity burden in postmenopausal patients.