CDK4/6 inhibitors have changed the treatment of metastatic hormone-receptor–positive breast cancer by significantly prolonging progression-free survival when given in combination with endocrine therapy.

More recently, data from 2 trials – MONALEESA-7 and PALOMA-3 – have indicated an overall survival benefit as well.1,2

In a recent issue of The New England Journal of Medicine, Hope S. Rugo, MD, of the University of California, San Francisco, discussed several lessons that could be taken from these trials, which all involved slightly different patient populations.3

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MONALEESA-7 included both premenopausal and perimenopausal women and showed a significant overall survival benefit for patients assigned to ribociclib compared with placebo (median not yet reached vs 40.9 months for placebo; P =.00973).

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“These remarkable results represent a major advance in the treatment of metastatic hormone-receptor–positive breast cancer, specifically in improving the outcome in young women, who are often excluded from trials of hormone therapies,” Dr Rugo wrote.

In PALOMA-3, there was no significant overall survival difference between patients assigned to receive palbociclib and fulvestrant compared with fulvestrant alone; however, Dr Rugo noted that “overall survival was 10 months longer in the 79% of patients who had had sensitivity to previous endocrine therapy than in the 21% who had not.”

Final overall survival data from PALOMA-2 are not yet available.4 This trial included postmenopausal women with bone-only disease and no previous chemotherapy, a population in contrast to that of MONALEESA-7. In PALOMA-2, a between-group survival difference was seen at a median follow-up of “just under 3 years, even though 18.6% of patients who discontinued the trial regimen in the placebo group received a CDK4/6 inhibitor as subsequent therapy,” Dr Rugo noted. 3

Among the lessons to be taken from these results, the doctor wrote, are that premenopausal women with induced menopause can be treated in the same way as naturally postmenopausal women, and that improvement in overall survival outcomes can be achieved in trials of targeted agents for hormone-receptor–positive metastatic disease.

“It is clear that the choice of the patient population and the use of effective therapies are critical,” Dr Rugo wrote. “On the basis of the MONALEESA-7 trial and other trials in the first-line setting, the standard of care should now include a CDK4/6 inhibitor as first-line treatment. We are redefining the standards and outcomes in metastatic disease; the treatment of early-stage disease is the next frontier.”3


  1. Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor–positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19:904-15.
  2. Im S-A, Lu Y-S, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019; 381:307-16.
  3. Rugo HS. Achieving improved survival outcomes in advanced breast cancer. N Engl J Med. 2019;doi:10.1056/NHJMe1906236.
  4. Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 2018;379:1926-36.