NICE Recommends Approval for Ribociclib, Palbociclib for HR+/ HER2- Advanced Breast Cancer

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The United Kingdom's National Institute for Health and Care Excellence has issued guidance supporting approval for ribociclib and palbociclib for patients with hormone receptor-positive/HER2-negative locally advanced or secondary breast cancer.

Carole Longson, PhD

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has issued guidance supporting approval for ribociclib (Kisqali) and palbociclib (Ibrance) for patients with hormone receptor-positive/HER2¬-negative locally advanced or secondary breast cancer.

Both CDK4/6 inhibitors are indicated for use with an aromatase inhibitor (AI). If approved for routine National Health Service (NHS) use, about 8000 newly diagnosed patients in the United Kingdom would be eligible for treatment with the CDK4/6 inhibitors. Ribociclib is produced by Novartis and palbociclib is a Pfizer product.

Carole Longson, PhD, NICE’s director of the center for health technology evaluation, said in a news release that the institute decided to recommend approval after drug manufacturers provided more evidence for their effectiveness and agreed to a lower price.

“The committee heard that by postponing disease progression, palbociclib and ribociclib may reduce the number of people who are exposed to the often unpleasant side effects of chemotherapy, and delay the need for its use in others,” Longson said. “We are pleased, therefore, that the companies have been able to agree [to] reductions to the price of palbociclib and ribociclib to allow them to be made routinely available to people with this type of breast cancer.”

The price of 1 cycle of treatment with either palbociclib or ribociclib is listed at £2,950 ($3950), but the discounted price remains confidential. NICE’s appraisal committee determined that both drugs meet thresholds for incremental cost-effectiveness ratio (ICER). The agency had previously rejected palbociclib as too expensive in relation to its clinical effectiveness.

In recommending ribociclib, the appraisal committee reviewed data from the phase III MONALEESA-7 trial.1 In the phase III study, 668 postmenopausal women with advanced breast cancer were randomized to letrozole plus ribociclib (n = 334) or placebo (n = 334). Letrozole was administered at 2.5 mg per day and ribociclib was given at 600 mg per day for 3 weeks followed by 1 week off.


In results first presented in January 2017, ribociclib plus letrozole improved progression-free survival (PFS) by 9.3 months compared with letrozole plus placebo. At a median follow-up of 26.4 months, the median PFS was 16.0 months (95% CI, 13.4-18.2) with letrozole plus placebo compared with 25.3 months (95% CI, 23.0-30.3) for ribociclib and letrozole, representing a 43% reduction in the risk of progression or death with the addition of the CDK4/6 inhibitor (HR, 0.568; 95% CI, 0.457-0.704; P <.0001). The 24-month PFS rate was 54.7% with ribociclib versus 35.9% for placebo.

Updated results were presented this month at the 2017 San Antonio Breast Cancer Symposium. The median PFS was 23.8 months for women who received ribociclib in combination with either tamoxifen or a nonsteroidal AI (HR, 0.553; 95% CI, 0.441-0.694; P <.0001).3

The committee reviewed data from the PALOMA-1 and PALOMA-2 trials in recommending palbociclib.4,5 In the phase II PALOMA-1, 165 postmenopausal patients with estrogen receptor (ER)-positive+/HER2-negative advanced breast cancer participated in the 2-part trial. Part 1 contained 66 patients and part 2 had 99 patients. Continuous daily letrozole was administered at 2.5 mg with or without palbociclib at 125 mg daily for 3 weeks followed by 1 week of rest until progression. The primary endpoint was PFS by investigator assessment.

At the final analysis, presented at the 2014 AACR Annual Meeting, the median overall survival (OS) was 37.5 months with palbociclib compared with 33.3 months with letrozole alone (HR, 0.813; 95% CI, 0.492-1.345; P = .2105). However, this first analysis of OS contained data from only 61 patients (37%) and was not deemed statistically significant.

In the double-blind placebo-controlled PALOMA-2 trial, 666 patients were randomly assigned to palbociclib plus letrozole or letrozole alone. Palbociclib was administered at 125 mg daily for 3 weeks in a 28-day cycle. Continuous letrozole was administered at 2.5 mg.5

The investigator-assessed median PFS with the palbociclib combination was 24.8 months versus 14.5 months with letrozole alone (HR, 0.58; 95% CI, 0.46-0.72; P <.0001). The median PFS by blinded independent central review was 30.5 months versus 19.3 months, respectively (HR, 0.65; 95% CI, 0.51-0.84; P = .0005). The objective response rate was 42% with the combination versus 35% in the control group. The PFS benefit with palbociclib was sustained across subgroups.

The European Union approved palbociclib in combination with an AI for frontline use in this population in November 2016 and did the same for ribociclib this August. The FDA approved ribociclib with an AI for frontline treatment of postmenopausal women with HR+/HER2— advanced breast cancer in March. The agency approved palbociclib in combination with letrozole (Femara) as a frontline treatment for postmenopausal women with ER+/HER2– metastatic breast cancer that same month.


  1. Hortobagyi GN, Stemmer SM, Burris HA, et al. First-line ribociclib + letrozole for postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract LBA1.
  2. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer [published online October 8, 2016]. N Engl J Med. doi:10.1056/NEJMoa1609709.
  3. Tripathy D, Sohn J, Im SA, et al. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the randomized phase III MONALEESA-7 trial. Presented at: the 2017 San Antonio Breast Cancer Symposium; Dec. 5-9, 2017. Abstract GS2-05.
  4. Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16(1):25—35.
  5. Finn RS, Martin M, Rugo HS, et al. PALOMA-2: Primary results from a phase III trial of palbociclib (P) with letrozole (L) compared with letrozole alone in postmenopausal women with ER+/HER2— advanced breast cancer (ABC). J Clin Oncol. 34, 2016 (suppl; abstr 507).