Research to treat metastatic relapse of the most common form of breast cancer in post-menopausal women.

Results after seven years follow up of the international PALOMA-2 trial have shown that the cyclin dependent kinase inhibitor palbociclib (Ibrance) used in conjunction with endocrine therapy, letrozole, to treat metastatic relapse of the most common form of breast cancer in post-menopausal women did not improve overall survival when compared with letrozole therapy alone. Whilst there was a numerical 2 month difference, it did not meet a predefined level of statistical significance.

Treatment using both palbociclib and letrozole has already been reported to nearly double progression-free survival in these women from a median 14.5 months to 27.6 months. At the American Society of Clinical Oncology Annual Meeting in Chicago last June, PALOMA-2 study researchers reported overall survival was 51.2 months with letrozole alone and 53.9 months using the dual therapy.

PALOMA-2 was the first trial to look at the impact of adding a cyclin-dependent kinase (CDK) inhibitor (palbociclib) to the standard treatment of an endocrine inhibitor (letrozole) in post-menopausal women with oestrogen receptor positive breast cancer that had relapsed as advanced or metastatic disease. The study enrolled 666 women, including 20 in Australia and New Zealand.

There are likely to be several reasons for the lack of statistical significance of the result, says medical oncologist Dr Janine Lombard of the Calvary Mater Newcastle Hospital.

As the Breast Cancer Trials (Australia New Zealand) principal investigator for the international study, Dr Lombard says missing data was a major concern.

“Unfortunately, by the time of the survival analysis, one-third of the patients were lost to follow-up. We don’t know what happened to them. But it meant that our statistics were not powerful enough to show a difference in survival,” she says. In the 10 years since the trial completed, however, two other drugs similar to palbociclib have come on the market, one of which improves overall survival in a very similar group of women with advanced hormone positive breast cancer, with the survival analysis of the other drug still pending.

“Palbociclib really does make a difference, however,” says Dr Lombard. “It doubles the time of cancer control, allowing more time for women needing to navigate to another therapy because the cancer has progressed. And it is very, very well tolerated, because it is not a chemotherapy. You don’t have any of the chemo toxicity, the hair loss and vomiting. In fact, for most women, the side effect profile is very favourable.”

Similar studies to PALOMA-2 have been undertaken with two other CDK inhibitors. Dr Lombard says the results mirror what has been found with Palbociclib and all significantly increase progression free survival.

These drugs all have slightly different side-effect profiles, which means if patients can’t tolerate one, there is now the confidence to switch to one of the others. “It is always good for patients if you have more than one tablet option.”


Richard Finn, Hope Rugo, Veronique Dieras, Nadia Harbeck, Seock-Ah Im, Karen Gelmon, Janice Walshe, Miguel Martin, Mariana MacGregor, Eustratius Bananis, Eric Gauthier, Dongrui Lu, Sindy Kim and Dennis Slamon (2022) Overall survival (OS) with first-line palbociclib plus letrozole (PAL+LET) versus placebo plus letrozole (PBO+LET) in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ER+/HER2−ABC): Analyses from PALOMA-2. Oral Abstract for American Society of Clinical Oncology meeting, Chicago https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA1003


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Dr Janine Lombard

The Breast Cancer Trials principal investigator for the international PALOMA-2 study, Dr Janine Lombard.

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