Palbociclib in Patients With Head and Neck Cancer and Other Tumors With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study
- Worden, Francis P. MD1,
- Pisick, Evan MD2
- Rothe, Michael MS3
- Mangat, Pam K. MS3,
- Garrett-Mayer, Elizabeth PhD3
- Khalil, Maged F. MD4
- Carrizosa, Daniel R. MD5,
- Bauman, Jessica R. MD6,
- Leidner, Rom S. MD7,
- Duvivier, Herbert L. MD8,
- Fu, Siqing MD, PhD9,
- Park, Min S. MD10,
- Yost, Kathleen J. MD11,
- Calfa, Carmen J. MD12
- Marr, Alissa S. MD13
- Balmanoukian, Ani S. MD14,
- Behl, Deepti MD15,
- Cannon, Timothy L. MD16,
- Nabell, Lisle MD17
- Powell, Steven Francis MD18,
- Thota, Ramya MBBS19
- Hinshaw, Dominique C. PhD3
- Gregory, Abigail MPH3,
- Grantham, Gina N. BS3
- Halabi, Susan PhD, FSCT, FASCO20,
- Schilsky, Richard L. MD, FACP, FSCT, FASCO3,
PURPOSE
Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Two cohorts of patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)–mutated tumors treated with palbociclib are reported: one with head and neck cancer (HNC) with both squamous and nonsquamous cell histologies, and one with histology-pooled (HP) cancers.
METHODS
Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. For the HNC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included OR, safety, progression-free survival, overall survival, duration of response, and duration of SD
RESULTS
Seventy patients with HNC (N = 28) or HP cancers (N = 42) were treated with palbociclib. For the HNC cohort, DC and OR rates were 40% (one-sided 90% CI, 27 to 100) and 4% (95% CI, <1 to 18), respectively. The null hypothesis was rejected (P = .002). For the HP cohort, DC and OR rates were 13% (one-sided 90% CI, 6 to 100) and 5% (95% CI, <1 to 17), respectively. The null hypothesis was not rejected. Thirty-one of 70 patients experienced treatment-related grade 3 to 4 adverse events (AEs) or serious AEs, the most common including neutropenia, thrombocytopenia, and leukopenia.
CONCLUSION
Palbociclib met prespecified criteria to declare a signal of activity in patients with HNC with CDKN2A alterations, but not in the HP cohort.