ASCO 2022 – Key Take-Aways in Breast Cancer. Are We Making Progress? Part 2
As discussed in our June 27 Science Spotlight (ASCO Highlights Part 1), where we reported on two breast cancer presentations, each year tens of thousands of researchers, advocates, and industry representatives come together for the American Society of Clinical Oncology (ASCO) annual conference to hear the latest in cancer research. In this Part 2, we summarize the long-awaited results of PALOMA-2, that showed no improvement in overall survival for palbociclib. These results underscore why NBCC is a staunch advocate of only approving drugs based on results that demonstrate clinical benefits to patients—either improvements in quality of life or length of survival.
The PALOMA-2 Study
Key Takeaway: There was no improvement in overall survival with the addition of palbociclib to endocrine therapy in the first line setting of ER+/HER2- metastatic breast cancer.
Background: There were two prior trials of palbociclib (IBRANCE®; a CDK4/6 inhibitor) in combination with letrozole (Femara®; an aromatase inhibitor). The first (PALOMA-1) resulted in accelerated approval of the drug in February 2015 based on a 10-month improvement in progression-free survival (PFS). The FDA subsequently granted regular approval of palbociclib in March 2017[i] based on the results of PALOMA-2, the trial that served as the confirmatory trial for the accelerated approval. The key endpoint in trial was again, PFS. The median PFS was 24.8 months in the palbociclib plus letrozole arm and 14.5 months in the placebo plus letrozole arm. At that time, data on overall survival (OS), a clinically meaningful though secondary endpoint of the study was immature. But palbociclib received regular approval anyway.
Dr. Richard Finn of the University of California, Los Angeles presented the final OS results from PALOMA-2[ii] at ASCO. After a median follow-up of 90 months (7.5 years), the median OS was 53.9 months in the treatment arm and 51.2 months in the placebo arm. While numerically higher this difference was not statistically significant (p=0.3378), which means the difference could be due to chance. Of note, the final OS data for PALOMA-1 published in 2020[iii], was also not statistically significant.
Much of the discussion that followed the presentation revolved around the lack of an overall survival improvement (in both PALOMA-1 and PALOMA-2) when compared with other approved CDK4/6 inhibitors (i.e., ribociclib [KISQALI®] and abemaciclib [Verzenio®]) which have demonstrated a PFS and OS benefit in patients with advanced or metastatic HR+/HER2- breast cancer. Some questioned whether known biological/functional differences among the drugs or the patient population included in the trials would account for the difference. We have written more about this previously when the drug was tested in the adjuvant setting for early HR+/HER2- breast cancer. The drug was not approved in early breast cancer. Read more here.
Regardless of the reason, at this point, there are no data that show that treatment with palbociclib, at a cost of ~$13,000 per month, lengthens the time that patients with advanced or metastatic HR+/HER2- breast cancer live.
Over the past 10 years, an increasing number of cancer drugs have been approved through the FDA’s accelerated approval on the basis of surrogate endpoints (e.g., progression free survival). These are endpoints that are supposed to have a high likelihood of leading to clinical benefit (e.g., overall survival) and confirmatory trials are supposed to confirm that benefit before the FDA grants regular approval. Far too often, confirmatory trials use surrogate endpoints as the primary endpoint, and drugs that have never demonstrated clinical benefit continue to be available or even receive regular approval without evidence of benefit.
As patients and advocates, we should demand confirmation of clinical benefit before we allow drugs to gain regular approval. If they don’t, their approval should be rescinded.
[i] https://www.fda.gov/drugs/resources-information-approved-drugs/palbociclib-ibrance
[ii] Finn RS, Rugo HS, Dieras VC, et al. 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. J Clin Oncol. 2022;40(suppl 17):LBA1003. doi:10.1200/JCO.2022.40.17_suppl.LBA1003
[iii] Finn RS, Boer K, Bondarenko I, et al. Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (PALOMA-1, TRIO-18). Breast Cancer Res Treat. 2020 Sep;183(2):419-428. doi: 10.1007/s10549-020-05755-7. Epub 2020 Jul 18. PMID: 32683565; PMCID: PMC7383036.
Introducing NBCC’s New Chief Operating Officer/Chief of Staff, Mara Walker
Mara Walker joined the National Breast Cancer Coalition as Chief Operating Officer/Chief of Staff in June 2022. Mara is a nonprofit leader with over 30 years of experience helping organizations and their people achieve their goals. She is the former Chief Operating Officer for Americans for the Arts where she was responsible for the overall performance of the organization, which included a 501(c)3 and (c)4. Mara, a native New Yorker, currently serves as Vice Chair of Theatre Washington, Chairing their Governance Committee, and has consulted on board development. She holds a B.A. in theatre from George Washington University and an M.F.A. in theatre management from the University of Maryland.
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