Utilization and Clinical Benefit of Immune Checkpoint Inhibitor in Veterans With Microsatellite Instability-High Prostate Cancer

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Background

The utilization of immune checkpoint inhibitors (ICI) in prostate cancer (PC) can be very effective for patients with mismatch repair-deficiency (as identified by MSI-H by PCR/NGS or dMMR IHC). The use of ICI in this patient population has been associated with high rates of durable response. There is limited published data on factors that may influence patient response and outcomes. The aim of this study is to describe the utilization of and tumor response to ICI in this patient population.

Methods

This is a retrospective study of men with MSI-H PC reported by somatic genomic testing from April 1, 2015 to March 31, 2022 through the VA National Precision Oncology Program (NPOP), who received at least one dose of ICI. The primary objectives are to describe the incidence of MSI-H PC and the utilization of ICI. Descriptive statistics and Kaplan- Meier estimator were used for secondary objectives to determine the prostate-specific antigen decline of at least 50% (PSA50), clinical progression free survival (cPFS), time on ICI as a function of number of prior therapies, the extent of metastasis prior to initiation of ICI, and the correlation of MMR genetic alterations with treatment response.

Results

66 patients with MSI-H PC were identified (1.5% of a total of 4267 patients with PC tested through NPOP). 23 patients (35%) received at least one dose of ICI. 12 of 23 patients (52%) had PSA response. PSA50 responses occurred in 6 patients (50%) and 5 continued to have durable PSA50 at six months. Median cPFS was 280 days (95% CI: 105 days-not reached) and the estimated PFS at six months was 72.2% (95% CI: 35.7%-90.2%). 8 of 12 (67%) responders have received multiple lines of therapy for M1 PC. 8 of 12 patients (67%) had high-volume disease at ICI initiation. Of those patients with a MMR genetic alteration, patients with MLH1 (3/3) and MSH2 (6/8) alterations responded more frequently than those with MSH6 alterations (1/4).

Conclusions

MSI-H PC is rare but response rates to ICI are high and durable. Patients with MLH1 and MSH2 alterations appeared to respond more frequently than those with MSH6. Additional follow-up is ongoing.

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Background

The utilization of immune checkpoint inhibitors (ICI) in prostate cancer (PC) can be very effective for patients with mismatch repair-deficiency (as identified by MSI-H by PCR/NGS or dMMR IHC). The use of ICI in this patient population has been associated with high rates of durable response. There is limited published data on factors that may influence patient response and outcomes. The aim of this study is to describe the utilization of and tumor response to ICI in this patient population.

Methods

This is a retrospective study of men with MSI-H PC reported by somatic genomic testing from April 1, 2015 to March 31, 2022 through the VA National Precision Oncology Program (NPOP), who received at least one dose of ICI. The primary objectives are to describe the incidence of MSI-H PC and the utilization of ICI. Descriptive statistics and Kaplan- Meier estimator were used for secondary objectives to determine the prostate-specific antigen decline of at least 50% (PSA50), clinical progression free survival (cPFS), time on ICI as a function of number of prior therapies, the extent of metastasis prior to initiation of ICI, and the correlation of MMR genetic alterations with treatment response.

Results

66 patients with MSI-H PC were identified (1.5% of a total of 4267 patients with PC tested through NPOP). 23 patients (35%) received at least one dose of ICI. 12 of 23 patients (52%) had PSA response. PSA50 responses occurred in 6 patients (50%) and 5 continued to have durable PSA50 at six months. Median cPFS was 280 days (95% CI: 105 days-not reached) and the estimated PFS at six months was 72.2% (95% CI: 35.7%-90.2%). 8 of 12 (67%) responders have received multiple lines of therapy for M1 PC. 8 of 12 patients (67%) had high-volume disease at ICI initiation. Of those patients with a MMR genetic alteration, patients with MLH1 (3/3) and MSH2 (6/8) alterations responded more frequently than those with MSH6 alterations (1/4).

Conclusions

MSI-H PC is rare but response rates to ICI are high and durable. Patients with MLH1 and MSH2 alterations appeared to respond more frequently than those with MSH6. Additional follow-up is ongoing.

Background

The utilization of immune checkpoint inhibitors (ICI) in prostate cancer (PC) can be very effective for patients with mismatch repair-deficiency (as identified by MSI-H by PCR/NGS or dMMR IHC). The use of ICI in this patient population has been associated with high rates of durable response. There is limited published data on factors that may influence patient response and outcomes. The aim of this study is to describe the utilization of and tumor response to ICI in this patient population.

Methods

This is a retrospective study of men with MSI-H PC reported by somatic genomic testing from April 1, 2015 to March 31, 2022 through the VA National Precision Oncology Program (NPOP), who received at least one dose of ICI. The primary objectives are to describe the incidence of MSI-H PC and the utilization of ICI. Descriptive statistics and Kaplan- Meier estimator were used for secondary objectives to determine the prostate-specific antigen decline of at least 50% (PSA50), clinical progression free survival (cPFS), time on ICI as a function of number of prior therapies, the extent of metastasis prior to initiation of ICI, and the correlation of MMR genetic alterations with treatment response.

Results

66 patients with MSI-H PC were identified (1.5% of a total of 4267 patients with PC tested through NPOP). 23 patients (35%) received at least one dose of ICI. 12 of 23 patients (52%) had PSA response. PSA50 responses occurred in 6 patients (50%) and 5 continued to have durable PSA50 at six months. Median cPFS was 280 days (95% CI: 105 days-not reached) and the estimated PFS at six months was 72.2% (95% CI: 35.7%-90.2%). 8 of 12 (67%) responders have received multiple lines of therapy for M1 PC. 8 of 12 patients (67%) had high-volume disease at ICI initiation. Of those patients with a MMR genetic alteration, patients with MLH1 (3/3) and MSH2 (6/8) alterations responded more frequently than those with MSH6 alterations (1/4).

Conclusions

MSI-H PC is rare but response rates to ICI are high and durable. Patients with MLH1 and MSH2 alterations appeared to respond more frequently than those with MSH6. Additional follow-up is ongoing.

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Outcomes of Off-Label Use of Molecular Targeted Agent Therapy in a Large-Scale Precision Oncology Program

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Background

Increasing utilization of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) has led to substantial improvements in outcomes among patients with cancer with actionable mutations. We sought to evaluate real-world use and outcomes of off-label TA among patients who underwent CGP.

Methods

The National Precision Oncology Program database and VA Corporate Data Warehouse were queried to identify patients who underwent CGP between Feb 2019 and Dec 2021 and were prescribed 1 of 73 TAs for malignancy. OncoKB (accessed March 2022) annotations were used to select patients who received offlabel TAs based upon CGP results. Chart abstraction was performed in April 2022 to review response to offlabel TAs, toxicities, and treatment duration.

Results

Of 18,686 patients who underwent CGP, 2,107 (11%) were prescribed a TA and 170 (0.9%) were prescribed a total of 185 off-label TA regimens. Median age was 68 years, 88% were male, and 82% had prior systemic therapy, with 28% receiving 3 or more prior lines. Frequency of off-label TA prescriptions was highest for patients with unknown primary (CUP) (9%), thyroid (8%), and breast (6%) cancers. Most frequently targeted alterations involved ERBB2 (22%), BRAF (22%), and BRCA1/BRCA2/ATM (20%). Among the 161 regimens prescribed > 4 weeks, 44 (27%) led to complete or partial response, and 63 (39%) were administered for 6 months or longer or are continuing. Median progression free (PFS) and overall survival (OS) were 5.3 (95% CI, 4.3–6.5) and 9.9 (95% CI, 8.3–12.4) months, respectively. Patients with OncoKb level 2/3A/3B annotations had improved PFS (HR 0.45; 95% CI, 0.24-0.82; P = .01) and OS (HR 0.27; 95% CI, 0.15-0.48; P < .005) compared to level 4 treatments. Across all 185 regimens prescribed, 30 (16.2%) were discontinued due to toxicity, and further systemic treatment was prescribed subsequently in 58 (31.3%).

Conclusions

While the overall use of off-label TAs is low, nearly 10% of CUP and thyroid cancer patients who undergo CGP are prescribed TAs for off-label indications. More than one-quarter of off-label TA regimens lead to treatment response. Treatments associated with level 4 annotations lead to worse outcomes than TAs bearing superior levels of evidence.

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Background

Increasing utilization of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) has led to substantial improvements in outcomes among patients with cancer with actionable mutations. We sought to evaluate real-world use and outcomes of off-label TA among patients who underwent CGP.

Methods

The National Precision Oncology Program database and VA Corporate Data Warehouse were queried to identify patients who underwent CGP between Feb 2019 and Dec 2021 and were prescribed 1 of 73 TAs for malignancy. OncoKB (accessed March 2022) annotations were used to select patients who received offlabel TAs based upon CGP results. Chart abstraction was performed in April 2022 to review response to offlabel TAs, toxicities, and treatment duration.

Results

Of 18,686 patients who underwent CGP, 2,107 (11%) were prescribed a TA and 170 (0.9%) were prescribed a total of 185 off-label TA regimens. Median age was 68 years, 88% were male, and 82% had prior systemic therapy, with 28% receiving 3 or more prior lines. Frequency of off-label TA prescriptions was highest for patients with unknown primary (CUP) (9%), thyroid (8%), and breast (6%) cancers. Most frequently targeted alterations involved ERBB2 (22%), BRAF (22%), and BRCA1/BRCA2/ATM (20%). Among the 161 regimens prescribed > 4 weeks, 44 (27%) led to complete or partial response, and 63 (39%) were administered for 6 months or longer or are continuing. Median progression free (PFS) and overall survival (OS) were 5.3 (95% CI, 4.3–6.5) and 9.9 (95% CI, 8.3–12.4) months, respectively. Patients with OncoKb level 2/3A/3B annotations had improved PFS (HR 0.45; 95% CI, 0.24-0.82; P = .01) and OS (HR 0.27; 95% CI, 0.15-0.48; P < .005) compared to level 4 treatments. Across all 185 regimens prescribed, 30 (16.2%) were discontinued due to toxicity, and further systemic treatment was prescribed subsequently in 58 (31.3%).

Conclusions

While the overall use of off-label TAs is low, nearly 10% of CUP and thyroid cancer patients who undergo CGP are prescribed TAs for off-label indications. More than one-quarter of off-label TA regimens lead to treatment response. Treatments associated with level 4 annotations lead to worse outcomes than TAs bearing superior levels of evidence.

Background

Increasing utilization of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) has led to substantial improvements in outcomes among patients with cancer with actionable mutations. We sought to evaluate real-world use and outcomes of off-label TA among patients who underwent CGP.

Methods

The National Precision Oncology Program database and VA Corporate Data Warehouse were queried to identify patients who underwent CGP between Feb 2019 and Dec 2021 and were prescribed 1 of 73 TAs for malignancy. OncoKB (accessed March 2022) annotations were used to select patients who received offlabel TAs based upon CGP results. Chart abstraction was performed in April 2022 to review response to offlabel TAs, toxicities, and treatment duration.

Results

Of 18,686 patients who underwent CGP, 2,107 (11%) were prescribed a TA and 170 (0.9%) were prescribed a total of 185 off-label TA regimens. Median age was 68 years, 88% were male, and 82% had prior systemic therapy, with 28% receiving 3 or more prior lines. Frequency of off-label TA prescriptions was highest for patients with unknown primary (CUP) (9%), thyroid (8%), and breast (6%) cancers. Most frequently targeted alterations involved ERBB2 (22%), BRAF (22%), and BRCA1/BRCA2/ATM (20%). Among the 161 regimens prescribed > 4 weeks, 44 (27%) led to complete or partial response, and 63 (39%) were administered for 6 months or longer or are continuing. Median progression free (PFS) and overall survival (OS) were 5.3 (95% CI, 4.3–6.5) and 9.9 (95% CI, 8.3–12.4) months, respectively. Patients with OncoKb level 2/3A/3B annotations had improved PFS (HR 0.45; 95% CI, 0.24-0.82; P = .01) and OS (HR 0.27; 95% CI, 0.15-0.48; P < .005) compared to level 4 treatments. Across all 185 regimens prescribed, 30 (16.2%) were discontinued due to toxicity, and further systemic treatment was prescribed subsequently in 58 (31.3%).

Conclusions

While the overall use of off-label TAs is low, nearly 10% of CUP and thyroid cancer patients who undergo CGP are prescribed TAs for off-label indications. More than one-quarter of off-label TA regimens lead to treatment response. Treatments associated with level 4 annotations lead to worse outcomes than TAs bearing superior levels of evidence.

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Identification of Clinically Actionable Genomic Alterations in Colorectal Cancer Patients From the VA National Precision Oncology Program (NPOP)

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Purpose

Colorectal cancer (CRC) is the fourth most common cancer at VA and the third leading cause of cancer-related death in the USA. The VA National Precision Oncology Program (NPOP) was established in 2016 with the goal of implementing standardized, streamlined methods for molecular testing of veterans with cancer and has enabled comprehensive genomic profiling (CGP) and precision medicine as part of routine cancer care. Obtaining CGP of predictive biomarkers in cancer tissue, including mutations in genes (e.g., KRAS, NRAS and BRAF), tumor mutation burden (TMB) and microsatellite instability status (MSI) can be used to support treatment decisions with targeted and immunotherapies.

Methods

In this study we describe the frequencies of these clinical biomarkers in colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), and other colon or rectum histologies (CROT); and compare these frequencies to a published cohort of metastatic CRC using Chi-square test (Yaeger et al., 2018).

Results

A total of 1802 patients with CRC were included in this study. COAD was the most frequent disease site (76.9%) followed by READ (19.1%). Approximately 52.9% of COAD patients harbored at least one highly actionable biomarker (defined as having an FDA-approved indication) including NRAS/ KRAS/BRAF wildtype (38.0%), TMB-H (12.9%), BRAF V600E (9.7%), MSI-H (8.9%), and NTRK fusion or rearrangement (0.3%). About 52.0% of patients with READ had these biomarkers, while this rate was (16.4%) in CROT. Among patients with COAD and READ, those with BRAF V600E mutations were more likely to be older, White, not Hispanic or Latino, and lived in urban areas compared to those without BRAF V600E. Relative to those with NRAS/KRAS/BRAF mutations, patients with NRAS/KRAS/BRAF wildtype were frequently younger. Relative to the frequency of biomarkers from a cBioPortal cohort of metastatic CRC, the frequency of NRAS wildtype was significantly lower in patients with COAD and READ tested through NPOP. 

Consulsions

In this cohort, ~53 % of patients with COAD and 52% of patients with READ have highly actionable biomarkers and are potentially eligible for FDAapproved targeted therapies. Future studies examining cancer outcomes with regard to the use of targeted therapies in the setting of actionable gene alterations, TMB, and MSI are warranted.

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Purpose

Colorectal cancer (CRC) is the fourth most common cancer at VA and the third leading cause of cancer-related death in the USA. The VA National Precision Oncology Program (NPOP) was established in 2016 with the goal of implementing standardized, streamlined methods for molecular testing of veterans with cancer and has enabled comprehensive genomic profiling (CGP) and precision medicine as part of routine cancer care. Obtaining CGP of predictive biomarkers in cancer tissue, including mutations in genes (e.g., KRAS, NRAS and BRAF), tumor mutation burden (TMB) and microsatellite instability status (MSI) can be used to support treatment decisions with targeted and immunotherapies.

Methods

In this study we describe the frequencies of these clinical biomarkers in colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), and other colon or rectum histologies (CROT); and compare these frequencies to a published cohort of metastatic CRC using Chi-square test (Yaeger et al., 2018).

Results

A total of 1802 patients with CRC were included in this study. COAD was the most frequent disease site (76.9%) followed by READ (19.1%). Approximately 52.9% of COAD patients harbored at least one highly actionable biomarker (defined as having an FDA-approved indication) including NRAS/ KRAS/BRAF wildtype (38.0%), TMB-H (12.9%), BRAF V600E (9.7%), MSI-H (8.9%), and NTRK fusion or rearrangement (0.3%). About 52.0% of patients with READ had these biomarkers, while this rate was (16.4%) in CROT. Among patients with COAD and READ, those with BRAF V600E mutations were more likely to be older, White, not Hispanic or Latino, and lived in urban areas compared to those without BRAF V600E. Relative to those with NRAS/KRAS/BRAF mutations, patients with NRAS/KRAS/BRAF wildtype were frequently younger. Relative to the frequency of biomarkers from a cBioPortal cohort of metastatic CRC, the frequency of NRAS wildtype was significantly lower in patients with COAD and READ tested through NPOP. 

Consulsions

In this cohort, ~53 % of patients with COAD and 52% of patients with READ have highly actionable biomarkers and are potentially eligible for FDAapproved targeted therapies. Future studies examining cancer outcomes with regard to the use of targeted therapies in the setting of actionable gene alterations, TMB, and MSI are warranted.

Purpose

Colorectal cancer (CRC) is the fourth most common cancer at VA and the third leading cause of cancer-related death in the USA. The VA National Precision Oncology Program (NPOP) was established in 2016 with the goal of implementing standardized, streamlined methods for molecular testing of veterans with cancer and has enabled comprehensive genomic profiling (CGP) and precision medicine as part of routine cancer care. Obtaining CGP of predictive biomarkers in cancer tissue, including mutations in genes (e.g., KRAS, NRAS and BRAF), tumor mutation burden (TMB) and microsatellite instability status (MSI) can be used to support treatment decisions with targeted and immunotherapies.

Methods

In this study we describe the frequencies of these clinical biomarkers in colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), and other colon or rectum histologies (CROT); and compare these frequencies to a published cohort of metastatic CRC using Chi-square test (Yaeger et al., 2018).

Results

A total of 1802 patients with CRC were included in this study. COAD was the most frequent disease site (76.9%) followed by READ (19.1%). Approximately 52.9% of COAD patients harbored at least one highly actionable biomarker (defined as having an FDA-approved indication) including NRAS/ KRAS/BRAF wildtype (38.0%), TMB-H (12.9%), BRAF V600E (9.7%), MSI-H (8.9%), and NTRK fusion or rearrangement (0.3%). About 52.0% of patients with READ had these biomarkers, while this rate was (16.4%) in CROT. Among patients with COAD and READ, those with BRAF V600E mutations were more likely to be older, White, not Hispanic or Latino, and lived in urban areas compared to those without BRAF V600E. Relative to those with NRAS/KRAS/BRAF mutations, patients with NRAS/KRAS/BRAF wildtype were frequently younger. Relative to the frequency of biomarkers from a cBioPortal cohort of metastatic CRC, the frequency of NRAS wildtype was significantly lower in patients with COAD and READ tested through NPOP. 

Consulsions

In this cohort, ~53 % of patients with COAD and 52% of patients with READ have highly actionable biomarkers and are potentially eligible for FDAapproved targeted therapies. Future studies examining cancer outcomes with regard to the use of targeted therapies in the setting of actionable gene alterations, TMB, and MSI are warranted.

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New Delivery Models Improve Access to Germline Testing for Patients With Advanced Prostate Cancer

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Objectives

The VA Oncology Clinical Pathway for Prostate Cancer is the first to include both tumor and germline testing to inform treatment and clinical trial eligibility for advanced disease. Anticipating increased germline testing demand, new germline testing delivery models were created to augment the existing traditional model of referring patients to genetics providers (VA or non-VA) for germline testing. The new models include: a non-traditional model where oncology clinicians perform all pre- and post-test activities and consult genetics when needed, and a hybrid model where oncology clinicians obtain informed consent and place e-consults for germline test ordering, results disclosure, and genetics follow-up, as needed. We sought to assess germline testing by delivery model.

Methods

Data sources included the National Precision Oncology Program (NPOP) dashboard and NPOP-contracted germline testing laboratories. Patient inclusion criteria: living as of 5/2/2021 with VA oncology or urology visits after 5/2/2021. We used multivariate regression to assess associations between patient characteristics and germline testing between 5/3/2021 (pathway launch) and 5/2/2022, accounting for clustering of patients within ordering clinicians.

Results

We identified 16,041 patients from 129 VA facilities with average age 75 years (SD, 8.2; range, 36- 102), 28.7% Black and 60.0% White. Only 5.6% had germline testing ordered by 60 clinicians at 67 facilities with 52.2% of orders by the hybrid model, 32.1% the non-traditional model, and 15.4% the traditional model. Patient characteristics positively associated with germline testing included care at hybrid model (OR, 6.03; 95% CI, 4.62-7.88) or non-traditional model facilities (OR, 5.66; 95% CI, 4.24-7.56) compared to the traditional model, completing tumor molecular testing (OR, 5.80; 95%CI, 4.98-6.75), and Black compared with White race (OR, 1.24; 95%CI, 1.06-1.45). Compared to patients aged < 66 years, patients aged 66-75 years and 76-85 years were less likely to have germline testing (OR, 0.74; 95%CI, 0.60-0.90; and OR, 0.67; 95%CI, 0.53-0.84, respectively).

Conclusions/Implications

Though only a small percentage of patients with advanced prostate cancer had NPOP-supported germline testing since the pathway launch, the new delivery models were instrumental to improving access to germline testing. Ongoing evaluation will help to understand observed demographic differences in germline testing. Implementation and evaluation of strategies that promote adoption of the new germline testing delivery models is needed. 0922FED AVAHO_Abstracts.indd 15 8

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Objectives

The VA Oncology Clinical Pathway for Prostate Cancer is the first to include both tumor and germline testing to inform treatment and clinical trial eligibility for advanced disease. Anticipating increased germline testing demand, new germline testing delivery models were created to augment the existing traditional model of referring patients to genetics providers (VA or non-VA) for germline testing. The new models include: a non-traditional model where oncology clinicians perform all pre- and post-test activities and consult genetics when needed, and a hybrid model where oncology clinicians obtain informed consent and place e-consults for germline test ordering, results disclosure, and genetics follow-up, as needed. We sought to assess germline testing by delivery model.

Methods

Data sources included the National Precision Oncology Program (NPOP) dashboard and NPOP-contracted germline testing laboratories. Patient inclusion criteria: living as of 5/2/2021 with VA oncology or urology visits after 5/2/2021. We used multivariate regression to assess associations between patient characteristics and germline testing between 5/3/2021 (pathway launch) and 5/2/2022, accounting for clustering of patients within ordering clinicians.

Results

We identified 16,041 patients from 129 VA facilities with average age 75 years (SD, 8.2; range, 36- 102), 28.7% Black and 60.0% White. Only 5.6% had germline testing ordered by 60 clinicians at 67 facilities with 52.2% of orders by the hybrid model, 32.1% the non-traditional model, and 15.4% the traditional model. Patient characteristics positively associated with germline testing included care at hybrid model (OR, 6.03; 95% CI, 4.62-7.88) or non-traditional model facilities (OR, 5.66; 95% CI, 4.24-7.56) compared to the traditional model, completing tumor molecular testing (OR, 5.80; 95%CI, 4.98-6.75), and Black compared with White race (OR, 1.24; 95%CI, 1.06-1.45). Compared to patients aged < 66 years, patients aged 66-75 years and 76-85 years were less likely to have germline testing (OR, 0.74; 95%CI, 0.60-0.90; and OR, 0.67; 95%CI, 0.53-0.84, respectively).

Conclusions/Implications

Though only a small percentage of patients with advanced prostate cancer had NPOP-supported germline testing since the pathway launch, the new delivery models were instrumental to improving access to germline testing. Ongoing evaluation will help to understand observed demographic differences in germline testing. Implementation and evaluation of strategies that promote adoption of the new germline testing delivery models is needed. 0922FED AVAHO_Abstracts.indd 15 8

Objectives

The VA Oncology Clinical Pathway for Prostate Cancer is the first to include both tumor and germline testing to inform treatment and clinical trial eligibility for advanced disease. Anticipating increased germline testing demand, new germline testing delivery models were created to augment the existing traditional model of referring patients to genetics providers (VA or non-VA) for germline testing. The new models include: a non-traditional model where oncology clinicians perform all pre- and post-test activities and consult genetics when needed, and a hybrid model where oncology clinicians obtain informed consent and place e-consults for germline test ordering, results disclosure, and genetics follow-up, as needed. We sought to assess germline testing by delivery model.

Methods

Data sources included the National Precision Oncology Program (NPOP) dashboard and NPOP-contracted germline testing laboratories. Patient inclusion criteria: living as of 5/2/2021 with VA oncology or urology visits after 5/2/2021. We used multivariate regression to assess associations between patient characteristics and germline testing between 5/3/2021 (pathway launch) and 5/2/2022, accounting for clustering of patients within ordering clinicians.

Results

We identified 16,041 patients from 129 VA facilities with average age 75 years (SD, 8.2; range, 36- 102), 28.7% Black and 60.0% White. Only 5.6% had germline testing ordered by 60 clinicians at 67 facilities with 52.2% of orders by the hybrid model, 32.1% the non-traditional model, and 15.4% the traditional model. Patient characteristics positively associated with germline testing included care at hybrid model (OR, 6.03; 95% CI, 4.62-7.88) or non-traditional model facilities (OR, 5.66; 95% CI, 4.24-7.56) compared to the traditional model, completing tumor molecular testing (OR, 5.80; 95%CI, 4.98-6.75), and Black compared with White race (OR, 1.24; 95%CI, 1.06-1.45). Compared to patients aged < 66 years, patients aged 66-75 years and 76-85 years were less likely to have germline testing (OR, 0.74; 95%CI, 0.60-0.90; and OR, 0.67; 95%CI, 0.53-0.84, respectively).

Conclusions/Implications

Though only a small percentage of patients with advanced prostate cancer had NPOP-supported germline testing since the pathway launch, the new delivery models were instrumental to improving access to germline testing. Ongoing evaluation will help to understand observed demographic differences in germline testing. Implementation and evaluation of strategies that promote adoption of the new germline testing delivery models is needed. 0922FED AVAHO_Abstracts.indd 15 8

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