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Barriers prevent patient access to personalized therapies identified by molecular tumor profiling of gynecologic malignancies.

Hillman RT, Ward K, Saenz C, McHale M, Plaxe S - J Pers Med (2015)

Bottom Line: Tumor profiling identified no clinically actionable mutations for seven patients (27%).Six patients sought insurance approval for a targeted therapy and two were declined (33%).One patient (4%) received a targeted therapy and this was discontinued due to tumor progression.

View Article: PubMed Central - PubMed

Affiliation: Rebecca and John Moores UCSD Cancer Center, Department of Reproductive Medicine, Division of Gynecologic Oncology, La Jolla, CA 92093, USA. rhillman@ucsd.edu.

ABSTRACT

Objective: This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies.

Methods: We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics.

Results: Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%). Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13). A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%). Six patients sought insurance approval for a targeted therapy and two were declined (33%). One patient (4%) received a targeted therapy and this was discontinued due to tumor progression.

Conclusions: There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials.

No MeSH data available.


Related in: MedlinePlus

Number and type of genetic alterations identified by tumor profiling. Six genes were mutated in multiple patient samples across the four most common tumor types in this series. Each box represents one patient sample. Mutation types include missense (red), splice site (green), nonsense (dark blue), frame shift (orange), amplification (yellow), and gene loss (light blue).
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jpm-05-00165-f001: Number and type of genetic alterations identified by tumor profiling. Six genes were mutated in multiple patient samples across the four most common tumor types in this series. Each box represents one patient sample. Mutation types include missense (red), splice site (green), nonsense (dark blue), frame shift (orange), amplification (yellow), and gene loss (light blue).

Mentions: FoundationOneTM (Foundation Medicine, Cambridge, MA, USA) tumor profiling identified a median of 3 genomic alterations per tumor sample (range 1 to 11 alterations). Significantly more genomic alterations were identified in tumor samples from endometrial adenocarcinomas (mean 10, 95% CI [8.27, 11.73]) than for all other tumor types (mean 3, 95% CI [2.43, 3.31]) (two-sample t-test, p < 0.0001). These genomic alterations included missense mutations, nonsense mutations, frame shifts, gene amplifications and gene deletions. The frequency and type of genomic alteration varied by tumor histology and gene locus (Figure 1). TP53 was the most frequently mutated gene locus with alterations noted in 46.1% of tumor samples (12 of 26), followed by KRAS mutations (9 of 26, 34.6%) and BRCA2 mutations (6 of 26, 23.0%).


Barriers prevent patient access to personalized therapies identified by molecular tumor profiling of gynecologic malignancies.

Hillman RT, Ward K, Saenz C, McHale M, Plaxe S - J Pers Med (2015)

Number and type of genetic alterations identified by tumor profiling. Six genes were mutated in multiple patient samples across the four most common tumor types in this series. Each box represents one patient sample. Mutation types include missense (red), splice site (green), nonsense (dark blue), frame shift (orange), amplification (yellow), and gene loss (light blue).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493494&req=5

jpm-05-00165-f001: Number and type of genetic alterations identified by tumor profiling. Six genes were mutated in multiple patient samples across the four most common tumor types in this series. Each box represents one patient sample. Mutation types include missense (red), splice site (green), nonsense (dark blue), frame shift (orange), amplification (yellow), and gene loss (light blue).
Mentions: FoundationOneTM (Foundation Medicine, Cambridge, MA, USA) tumor profiling identified a median of 3 genomic alterations per tumor sample (range 1 to 11 alterations). Significantly more genomic alterations were identified in tumor samples from endometrial adenocarcinomas (mean 10, 95% CI [8.27, 11.73]) than for all other tumor types (mean 3, 95% CI [2.43, 3.31]) (two-sample t-test, p < 0.0001). These genomic alterations included missense mutations, nonsense mutations, frame shifts, gene amplifications and gene deletions. The frequency and type of genomic alteration varied by tumor histology and gene locus (Figure 1). TP53 was the most frequently mutated gene locus with alterations noted in 46.1% of tumor samples (12 of 26), followed by KRAS mutations (9 of 26, 34.6%) and BRCA2 mutations (6 of 26, 23.0%).

Bottom Line: Tumor profiling identified no clinically actionable mutations for seven patients (27%).Six patients sought insurance approval for a targeted therapy and two were declined (33%).One patient (4%) received a targeted therapy and this was discontinued due to tumor progression.

View Article: PubMed Central - PubMed

Affiliation: Rebecca and John Moores UCSD Cancer Center, Department of Reproductive Medicine, Division of Gynecologic Oncology, La Jolla, CA 92093, USA. rhillman@ucsd.edu.

ABSTRACT

Objective: This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies.

Methods: We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics.

Results: Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%). Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13). A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%). Six patients sought insurance approval for a targeted therapy and two were declined (33%). One patient (4%) received a targeted therapy and this was discontinued due to tumor progression.

Conclusions: There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials.

No MeSH data available.


Related in: MedlinePlus