Pfizer was the first to release a drug for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer. However, Lilly is expected to make a new treatment history with more substantial clinical data of Verzenio, observers said.

Pfizer and Lilly released phase-3 clinical trial results on Ibrance (palbociclib) and Verzenio (abemaciclib), respectively, as a postoperative adjuvant therapy to achieve complete remission. However, their results were sharply divided.

Pfizer unveiled the outcome of the PALLAS study on May 29, saying that an independent Data Monitoring Committee (DMC) concluded that Ibrance was unlikely to show a statistically significant improvement in the primary endpoint.

The PALLAS study compared Ibrance plus standard adjuvant endocrine therapy to standard adjuvant endocrine therapy alone in 5,794 patients with HR+/HER2- early breast cancer in stage 2 and 3.

However, Ibrance failed to reach the primary endpoint of invasive disease-free survival (iDFS).

Pfizer said it was disappointed with the results, but the company would seek patients in many subgroups of the massive PALLAS study to see if they could benefit from Ibrance.

The failure of the PALLAS trial turned the industry’s attention to Lilly’s MonarchE study.

As cyclin-dependent kinase 4/6 (CDK4/6) inhibitors were known as a game-changer for the treatment of metastatic HR+/HER2- breast cancer, experts have anticipated that CDK4/6 inhibitors would also work on early breast cancer.

Lilly’s announcement of the interim results of the MonarchE on Tuesday rekindled the attention on CDK4/6 inhibitors.

Lilly said Verzenio met the primary endpoint in the study, showing that a CDK4/6 inhibitor could be beneficial in reducing the risk of relapse and death in early breast cancer.

The MonarchE study was also a large-scale trial on 4,580 patients, with the primary endpoint set as iDFS, just like the PALLAS trial.

Its difference from the PALLAS study was that Lilly’s trial recruited only high-risk patients.

Patients who participated in the MonarchE study had four or more positive axillary lymph nodes, tumor size of at least 5 cm, Grade 3 defined at least 8 points on the Bloom Richardson grading system, or those with over 20 percent of Ki-67 index. In other words, the participants had a relatively high risk of relapse.

With the strategic selections of target patients, Lilly’s Verzenio is likely to be the first CKD4/6 indicator to expand the indication for early breast cancer.

Another rival, Kisqali, by Novartis (ribociclib), is also being tested for the same indication.

The trial has the same kind of patients as those of the PALLAS study and aims to reach the primary endpoint by late 2025, according to ClinicalTrials.gov.

Pfizer’s Ibrance was the first CDK4/6 inhibitor but is likely to lose the battle against latecomer rivals in improving overall survival and showing postoperative adjuvant effect in metastatic breast cancer.

kym@docdocdoc.co.kr

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