Molecular Profile Detail

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Profile Name PALB2 inact mut
Gene Variant Detail

PALB2 inact mut (loss of function)

Relevant Treatment Approaches PARP Inhibitor (Pan)

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
PALB2 inact mut Advanced Solid Tumor sensitive PARP Inhibitor (Pan) Olaparib Preclinical Actionable In a preclinical study, Lynparza (olaparib) resulted in decreased cell survival in a PALB2 deficient cell line derived from a Fanconi anemia patient (PMID: 20871615). 20871615
PALB2 inact mut pancreatic ductal adenocarcinoma no benefit PARP Inhibitor (Pan) Cisplatin + Gemcitabine + Veliparib Phase II Actionable In a Phase II trial, the addition of Veliparib (ABT-888) to Gemzar (gemcitabine) and Platinol (cisplatin) in pancreatic ductal adenocarcinoma patients with either a germline BRCA1, BRCA2, or PALB2 inactivating mutation did not improve response rate (RR) compared to Gemzar (gemcitabine) and Platinol (cisplatin) alone, with 74.1% (20/27) vs 65.2% (15/23), P=0.55, and led to similar median progression-free survival, 10.1 vs 9.7 mo, P=0.73, and median overall survival, 15.5 vs 16.4 mo, P=0.6 (PMID: 31976786). 31976786
PALB2 inact mut prostate cancer sensitive PARP Inhibitor (Pan) Olaparib Phase II Actionable In a Phase II (TOPARP-B) trial, Lynparza (olaparib) treatment resulted in a composite overall response rate of 57.1% (4/7) and a RECIST objective response rate of 33.3% (2/6) in patients with castration-resistant prostate cancer harboring deleterious PALB2 mutations (PMID: 31806540; NCT01682772). 31806540
PALB2 inact mut prostate cancer predicted - sensitive PARP Inhibitor (Pan) Rucaparib Case Reports/Case Series Actionable In a Phase II trial (TRITON2), 2 of 2 patients with metastatic castrate-resistant prostate cancer harboring deleterious PALB2 alterations demonstrated a PSA response after treatment with Rubraca (rucaparib), with one of those patients demonstrating partial radiographic response that was ongoing 3.9 months, and the other a 47% reduction in tumor volume (PMID: 32086346; NCT02952534). 32086346
PALB2 inact mut prostate cancer sensitive PARP Inhibitor (Pan) Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including PALB2 (PMID: 32343890; NCT02987543). detail... detail... 32343890
PALB2 inact mut prostate cancer sensitive PARP Inhibitor (Pan) Olaparib Guideline Actionable Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in PALB2 (NCCN.org). detail...
PALB2 inact mut breast cancer predicted - sensitive PARP Inhibitor (Pan) Olaparib Phase II Actionable In a Phase II trial (TBCRC 048), Lynparza (olaparib) treatment resulted in an objective response rate (ORR) of 33% (9/27) and a clinical benefit rate (CBR) at 18 weeks of 50% in patients with metastatic breast cancer harboring germline mutations in homologous recombination-related genes other than BRCA1/2, all responders harbored germline PALB2 inactivating mutations, ORR and CBR in PALB2-mutant patients (n=11) were 82% and 100%, respectively (PMID: 33119476; NCT03344965). 33119476
PALB2 inact mut Her2-receptor negative breast cancer predicted - sensitive PARP Inhibitor (Pan) Talazoparib Case Reports/Case Series Actionable In a Phase II trial, Talzenna (talazoparib) treatment was well tolerated, and among 12 evaluable ERBB2 (HER2)-negative breast cancer patients with a homologous repair pathway mutation resulted in response in 25% (3/12) of patients, including two patients with germline mutations in PALB2, and resulted in stable disease for >/= 6 months in 3 patients, including one patient with a germline PALB2 mutation (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3006). detail...
PALB2 inact mut estrogen-receptor positive breast cancer sensitive PARP Inhibitor (Pan) Olaparib Guideline Actionable Lynparza (olaparib) is included in guidelines as second-line therapy for patients with ESR1 (ER)-positive, ERBB2 (HER2)-negative metastatic breast cancer with germline or somatic pathogenic/likely pathogenic PALB2 mutations who have progressed on an endocrine therapy plus CDK4/6 inhibitor (PMID: 34678411; ESMO.org). detail... 34678411
PALB2 inact mut estrogen-receptor positive breast cancer sensitive PARP Inhibitor (Pan) Talazoparib Guideline Actionable Talzenna (talazoparib) is included in guidelines as second-line therapy for patients with ESR1 (ER)-positive, ERBB2 (HER2)-negative metastatic breast cancer with germline or somatic pathogenic/likely pathogenic PALB2 mutations who have progressed on an endocrine therapy plus CDK4/6 inhibitor (PMID: 34678411; ESMO.org). 34678411 detail...
PALB2 inact mut pancreatic cancer predicted - sensitive PARP Inhibitor (Pan) Rucaparib Case Reports/Case Series Actionable In a Phase II trial, maintenance Rubraca (rucaparib) resulted in a median progression-free survival (mPFS) of 13.1 months and an objective response rate (ORR) of 41.7% (15/36, 3 complete responses, 12 partial responses) in patients with platinum-sensitive, advanced pancreatic cancer harboring deleterious mutations in BRCA1/2 or PALB2, ORR was 50% (3/6) in patients with PALB2 mutations (PMID: 33970687; NCT03140670). 33970687
PALB2 inact mut prostate cancer predicted - sensitive PARP Inhibitor (Pan) Abiraterone + Niraparib + Prednisone Phase III Actionable In a Phase III trial (MAGNITUDE), Zejula (niraparib) in combination with Zytiga (abiraterone) and Adasone (prednisone) (AAP) improved radiographic progression-free survival (HR 0.59) compared to placebo and AAP in patients with metastatic castration-resistant prostate cancer harboring inactivating mutations in the homologous recombination repair (HRR)-Fanconi pathway (BRIP1, FANCA, PALB2), with a HR of 0.59 in patients with PALB2 mutations (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 5020; NCT03748641). detail...
PALB2 inact mut pancreatic ductal adenocarcinoma sensitive Cisplatin + Gemcitabine Phase II Actionable In a Phase II trial, patients with pancreatic ductal adenocarcinoma harboring either a germline BRCA1, BRCA2, or PALB2 inactivating mutation demonstrated a response rate of 65.2% (15/23), a median progression-free survival of 9.7 months, a median overall survival of 16.4 months, and a disease control rate of 78.3% (18/23) when treated with a combination of Gemzar (gemcitabine) and Platinol (cisplatin) (PMID: 31976786). 31976786
PALB2 inact mut biliary tract cancer sensitive PARP Inhibitor (Pan) Rucaparib Guideline Actionable Rubraca (rucaparib) is included in guidelines as second or later-line therapy for patients with biliary tract cancer harboring BRCA1/2 mutations (PMID: 36372281; ESMO.org). detail... 36372281
PALB2 inact mut prostate cancer sensitive PARP Inhibitor (Pan) Enzalutamide + Talazoparib FDA approved Actionable In a Phase III trial (TALAPRO-2) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median radiographic progression-free survival compared to enzalutamide plus placebo (27.9 vs 16.4 mo, HR 0.46, p=0.0003) in patients with metastatic castration-resistant prostate cancer harboring deficient homologous recombination repair genes including PALB2, with an HR of 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197). 37285865 detail...
PALB2 inact mut prostate cancer sensitive PARP Inhibitor (Pan) Enzalutamide + Talazoparib Guideline Actionable Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic PALB2 mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org). detail...
PALB2 inact mut triple-receptor negative breast cancer predicted - sensitive PARP Inhibitor (Pan) Ceralasertib + Olaparib Case Reports/Case Series Actionable In a Phase II trial (plasmaMATCH), treatment with the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in limited efficacy in patients with advanced triple-negative breast cancer, with an objective response rate of 17.1% (12/70), including a complete response in a patient with a germline mutation in PALB2 (PMID: 37773077; NCT03182634). 37773077
PALB2 inact mut Her2-receptor negative breast cancer sensitive PARP Inhibitor (Pan) Olaparib Guideline Actionable Lynparza (olaparib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as second-line therapy for patients with hormone receptor-positive, ERBB2 (HER2)-negative metastatic breast cancer with germline pathogenic/likely pathogenic PALB2 mutations who have progressed on an endocrine therapy plus CDK4/6 inhibitor (PMID: 37178669; ESMO.org). 37178669 detail...
PALB2 inact mut prostate cancer predicted - sensitive PARP Inhibitor (Pan) unspecified PARP inhibitor Clinical Study - Meta-analysis Actionable In a combined analysis of 6 clinical trials, PARP inhibitor therapy improved radiographic progression-free survival (14 vs 9 mo, HR 0.52) and overall survival (25 vs 20 mo, HR 0.78) compared to placebo when combined with AR pathway inhibitors in patients with metastatic castration-resistant prostate cancer harboring PALB2 mutations, and resulted in an objective response rate of 14% (1/7) as monotherapy (PMID: 38484203; NCT02987543, NCT03732820, NCT03395197, NCT03748641, NCT02952534, NCT03148795). 38484203