Palbociclib plus letrozole on par with paclitaxel for early breast cancer

Dual anti-HER2 blockade with a chemotherapy-free backbone of palbociclib plus letrozole may serve as an alternative treatment to patients with HR-positive/HER2-positive early breast cancer, suggests the phase II TOUCH study, noting similar rates of pathological complete response (pCR) to that of paclitaxel.

One hundred forty-seven patients (median age 69 years) were randomized to receive paclitaxel (n=74) or palbociclib plus letrozole (n=73), both with trastuzumab plus pertuzumab (HP). More patients completed treatment with palbociclib than paclitaxel (94.4 percent vs 79.5 percent).

Neutropenia (6.9 percent in the paclitaxel plus HP arm vs 43.1 percent in the palbociclib plus letrozole plus HP arm) and diarrhoea (11 percent vs 8.3 percent) were the most common grade 3/4 adverse events documented.

The pCR rate was higher in the palbociclib plus letrozole group at 33.3 percent (95 percent CI, 22.7‒45.4) compared with 32.9 percent (95 percent CI, 22.3‒44.9) in the paclitaxel group.

The investigators did not see a significant treatment-by-RBsig* interaction (p=0.18): pCR in RBsig high vs low was 31.3 percent vs 42.3 percent in the paclitaxel group and 38.5 percent vs 25.8 percent in the palbociclib group. Moreover, pCR was higher in nonluminal vs luminal subtypes (45.5 percent vs 18.4 percent), with no interaction with treatment.

TOUCH is a phase II open-label trial for postmenopausal patients with cT >1 cm, cN0 or cN1, HR-positive/HER2-positive breast cancer, who received 16 weeks of neoadjuvant weekly paclitaxel or palbociclib and letrozole plus HP.

The authors examined the interaction between RBsig and pCR, hypothesizing higher pCR for RBsig-high tumours in the paclitaxel group and RBsig-low tumours in the palbociclib plus letrozole group. They assessed RBsig using RNA-sequencing from pretreatment biopsies and estimated intrinsic subtypes.

*gene signature of E2F pathway activity