Real-world data from a Molecular Tumor Board: improved outcomes in gynecologic and breast cancer patients with precision medicine

Abstract

Objectives: Next-generation sequencing (NGS) is being increasingly utilized in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide an N-of-One approach in order to maximize matched treatment; however, outcome data are limited. We evaluate the effect of the degree of matching patients to treatment and concordance with MTB recommendations on oncologic outcomes, including overall response rate (ORR), clinical benefit rate (CBR) (stable disease ≥6 months/partial or complete remission), progression-free survival (PFS), and overall survival (OS). Methods: 164 consecutive gynecologic and breast cancer patients presented at MTB from December 2012-September 2018 were assessed for clinicopathologic data, NGS results, MTB recommendations, therapy received, and oncologic outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment out of total number of pathogenic alterations, and concordance with MTB recommendations were analyzed in context of oncologic outcomes. Disease site, age, and number of prior lines of therapy were considered as covariates in univariate analysis and included in multivariate analysis if p<0.2. Results: 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS > 40% had higher ORR (30.8% vs. 7.1%; p=0.001) and CBR (73.1% vs. 31.2%; p<0.001) (Figure 1), PFS (HR 0.51, 95% CI 0.31, 0.85; p=0.002), and a trend toward improved OS (HR=0.64, 95% CI 0.34, 1.25; p=0.082) in univariate analysis. Higher MS was associated with improved ORR (HR 5.9, 95% CI 1.8, 19.0; p=0.003), CBR (HR 4.8, 95% CI 1.7, 13.4; p=0.003), and PFS (HR 0.5, 95% CI 0.3, 0.8; p=0.006) in multivariate analyses. Higher concordance with MTB recommendations was significantly associated with improved median PFS (9.0 months for complete concordance; 6.0 months for partial concordance; 4.0 months for no concordance; p=0.004) and OS (17.1 months complete concordance, 17.8 months partial concordance, 10.8 months no concordance; p=0.046). Patients who received completely MTB-concordant treatment had higher MS (p<0.001). In multivariate analysis comparing all vs none for concordance with MTB recommendations, PFS (HR 9.5; 95% CI 2.6, 35.0; p=0.001) and OS (HR 8.8, 95% CI 2.4, 33.2; p=0.001) remained significant. Conclusions: Concordance with MTB recommendations resulted in higher degrees of matched therapy and was associated with improved oncologic outcomes in gynecologic and breast cancer patients. Next-generation sequencing (NGS) is being increasingly utilized in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide an N-of-One approach in order to maximize matched treatment; however, outcome data are limited. We evaluate the effect of the degree of matching patients to treatment and concordance with MTB recommendations on oncologic outcomes, including overall response rate (ORR), clinical benefit rate (CBR) (stable disease ≥6 months/partial or complete remission), progression-free survival (PFS), and overall survival (OS). 164 consecutive gynecologic and breast cancer patients presented at MTB from December 2012-September 2018 were assessed for clinicopathologic data, NGS results, MTB recommendations, therapy received, and oncologic outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment out of total number of pathogenic alterations, and concordance with MTB recommendations were analyzed in context of oncologic outcomes. Disease site, age, and number of prior lines of therapy were considered as covariates in univariate analysis and included in multivariate analysis if p<0.2. 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS > 40% had higher ORR (30.8% vs. 7.1%; p=0.001) and CBR (73.1% vs. 31.2%; p<0.001) (Figure 1), PFS (HR 0.51, 95% CI 0.31, 0.85; p=0.002), and a trend toward improved OS (HR=0.64, 95% CI 0.34, 1.25; p=0.082) in univariate analysis. Higher MS was associated with improved ORR (HR 5.9, 95% CI 1.8, 19.0; p=0.003), CBR (HR 4.8, 95% CI 1.7, 13.4; p=0.003), and PFS (HR 0.5, 95% CI 0.3, 0.8; p=0.006) in multivariate analyses. Higher concordance with MTB recommendations was significantly associated with improved median PFS (9.0 months for complete concordance; 6.0 months for partial concordance; 4.0 months for no concordance; p=0.004) and OS (17.1 months complete concordance, 17.8 months partial concordance, 10.8 months no concordance; p=0.046). Patients who received completely MTB-concordant treatment had higher MS (p<0.001). In multivariate analysis comparing all vs none for concordance with MTB recommendations, PFS (HR 9.5; 95% CI 2.6, 35.0; p=0.001) and OS (HR 8.8, 95% CI 2.4, 33.2; p=0.001) remained significant. Concordance with MTB recommendations resulted in higher degrees of matched therapy and was associated with improved oncologic outcomes in gynecologic and breast cancer patients.