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| Ref Type | Journal Article | ||||||||||||
| PMID | (42456088) | ||||||||||||
| Authors | Veljovich DS, Rothe M, Garrett-Mayer E, Ali-Ahmad HM, Naumann RW, Siedel J, Chan JK, Gregory A, Pisick E, Adesunloye B, Arend RC, Bell M, Frimer M, Tawfik B, Thota R, Tsimberidou AM, Mangat PK, Hinshaw DC, Gregory A, Grantham GN, Halabi S, Schilsky RL | ||||||||||||
| Title | Palbociclib in Patients With Ovarian Cancer With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study. | ||||||||||||
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| Abstract Text | The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations. Results of a cohort of patients with ovarian cancer (OC) with CDKN2A alterations treated with palbociclib are reported.Eligible patients had advanced OC, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with CDKN2A alterations, and no remaining 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 (SD16+). Simon two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety.Twenty-eight patients were enrolled from February 2017 to April 2023, and all had OC with a CDKN2A alteration (loss [n = 21], mutation [n = 5], and loss and mutation [n = 2]). One patient was not evaluable for efficacy because of an excluded genomic finding. Three patients had a partial response and seven had SD16+ for DC and OR rates of 38% (90% CI, 25 to 100) and 11% (95% CI, 2 to 29), respectively. The null hypothesis of 15% DC rate was rejected (P = .004). The median PFS was 8 weeks (95% CI, 8 to 18) and the median OS was 33 weeks (95% CI, 24 to 73). Nineteen patients (68%) had at least one treatment-related grade 3-4 adverse event (AE) or serious AE including anemia, dyspnea, fatigue, leukopenia, neutropenia, and thrombocytopenia.Palbociclib met the prespecified criteria to declare a signal of activity in patients with OC and CDKN2A alterations. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| CDKN2A loss | ovarian cancer | sensitive | Palbociclib | Phase II | Actionable | In a Phase II trial (TAPUR), treatment with Ibrance (palbociclib) resulted in a disease control rate of 38% (10/27, 3 partial responses, 7 stable disease greater than 16 weeks), objective response rate of 11% (3/27), median progression-free survival of 8 weeks, and median overall survival of 33 weeks in patients with ovarian cancer harboring a CDKN2A alteration including loss (n=21), mutation (n=5), or both (n=2) (PMID: 42456088; NCT02693535). | 42456088 |