Shah, Anish

e20551 Background: Lung cancer is leading cause of cancer related mortality globally, with non-small cell lung cancer (NSCLC) comprising approximately 80% of all cases. The combination of immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1), specifically Durvalumab, and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors, such as Tremelimumab has demonstrated clinical efficacy in both adjuvant and neoadjuvant settings. However, a comprehensive systematic review of the available data is currently lacking. This study aims to assess the therapeutic efficacy of Durvalumab combined with Tremelimumab in NSCLC focusing on key end points including progression-free survival, overall survival, overall response rate, and safety, with particular attention to any adverse events and mortality. Methods: A comprehensive literature search was performed to identify relevant studies published until March 2024 across PubMed, Google Scholar, and Embase databases. Outcomes were pooled using the random effects DerSimonian-Laird model and reported as hazard ratio (HR) with a 95% confidence interval. A p-value of less than 0.05 was considered statistically significant. Results: A total of 1600 patients with NSCLC were included in the analysis, with 825 patients receiving Durvalumab plus Tremelimumab, and 775 patient receiving Standard chemotherapy across four studies. For Efficacy, following parameters were statistically significant: Progression Free Survival HR 0.75, 95%CI: 0.59, 0.92; Overall Survival HR 0.8, 95%CI: 0.58, 0.99; Overall Response Rate HR: 0.68, 95%CI: 0.47, 0.88, Mean Duration of Response was 12.23 month. Safety outcomes revealed that Durvalumab plus Tremelimumab versus Standard chemotherapy were comparable in mean percentage in terms of following parameters: Any Adverse Event (85.1% vs 92.8%), Any Serious Adverse Event (28.9% vs 17.75%), any mortality (6.35% vs 3.4%), Adverse Event leading to discontinuation (11.6% vs 10.13%), Any treatment related adverse event (69.96% vs 85.6%) and Any Treatment Related Death (0.9% vs 0.3%). Conclusions: Efficacy outcomes in patients treated with Durvalumab plus Tremelimumab demonstrated clinically meaningful improvements while the safety profile was comparable to that of Standard chemotherapy. Given the increasing use of this combination therapy as adjuvant and neoadjuvant treatment for NSCLC, further clinical trials are warranted to confirm and validate these findings.

Abstract Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Methods: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p<0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p=0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p<0.001). Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.

Abstract BACKGROUND: The OncotypeDX assay analyzes the expression of 21 genes, including HER2 and Grb7, to assess the predictive effect of chemotherapy in breast cancer recurrence among women with early-stage estrogen-receptor (ER) positive/HER2-negative breast cancer. In this study, we evaluate the distribution of recurrence score from the OncotypeDX assay based on the HER2 expression status by immunohistochemistry (IHC). METHODOLOGY: Utilizing the National Cancer Database, we identified adult women with a diagnosis of stage I – III ER+/HER2- invasive ductal carcinoma of the breast between the years 2010 and 2018. Recurrence scores were classified into low (&lt; 11), intermediate (11-26), and high risk (&gt;26); and the distribution of these recurrence scores cross-tabulated with different IHC scores of HER2 expression (0, 1+, and 2+) by IHC. Women with an IHC score of 2+ had to be negative for HER2 gene amplification by FISH. Multivariate logistic regression model adjusting for age, race, origin, progesterone receptor status, grade, and cancer stage was used to assess the odds of receiving a high OncotypeDx Score (≥26). RESULT: Among 198,931 women with ER+/HER2 negative breast cancer, 59,632 (30.0%) had HER2 IHC score of 0, 102,170 (51.4%) had IHC score of 1+, and 37,129 (18.6%) women were with IHC score of 2+. The median age at diagnosis of breast cancer among all three categories of HER2 expression was 59 years. The median recurrence score for women with IHC scores of 0,1+, and 2+ was 15, 15, and 16 respectively (p &lt; 0.001). A higher proportion of women with HER2 IHC score of 2+ had a high recurrence score compared to women with an IHC score of 0 (15.2% vs. 13%, p &lt; 0.001). In multivariate analysis, compared to women with HER2 IHC score of 0, women with HER2 IHC score of 2+/FISH negative were observed to have higher Odds (OR: 1.16; 95% CI: 1.11 – 1.20, p &lt; 0.001) of receiving high recurrence score. There was no significant difference in the odds of receiving a high recurrence score between women with IHC 0+ and 1+(OR: 0.99; 95% CI: 0.96 – 1.03, p 0.82). CONCLUSION: Women with a HER2 IHC score of 2+ were observed to have a higher odds of receiving high-risk recurrence scores as compared to women with IHC score of 0. This needs to be further correlated with the response to chemotherapy and the risk of recurrence. Citation Format: Anish Shah, Pravash Budhathoki, Suman Gaire, Utsav Joshi, Siddhartha Yadav. Influence of HER2 expression status in the distribution of recurrence score from the OncotypeDx assay among women with early-stage estrogen-receptor-positive/HER2-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-41.

Abstract Background: HER2-positive invasive lobular carcinoma (ILC) of the breast is a rare entity. Treatment decisions for HER2-positive lobular breast cancer are often extrapolated from the HER2-positive ductal subtype of breast cancer but the clinical outcomes and prognostic factors are not well defined. Methodology: Women with a diagnosis of stage I to III HER2-positive ILC or invasive ductal carcinoma (IDC) of the breast between 2010 and 2018 were identified from the National Cancer Database. Baseline characteristics were compared between ILC and IDC using Chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. Five-year overall survival (OS) was estimated by the Kaplan Meir method. Multivariate cox proportional hazards regression model including age, race, ethnicity, Charleston Deyo score, grade, TNM stage, and treatment modalities such as type of surgery, chemotherapy, and radiation was used to identify factors associated with OS in HER2-positive ILC. In a subset of patients receiving neoadjuvant chemotherapy, the odds of achieving a complete pathological response were compared between women with ILC and IDC in a multivariate logistic regression model adjusting for age, race, ethnicity, Charleston Deyo score, grade, and clinical stage. Results: A total of 4,197 women with HER2-positive ILC and 116,984 women with HER2-positive IDC were included in the final analysis. The median age at diagnosis was 63 years for women with HER2-positive ILC and 56 years for women with HER2-positive IDC (p&lt; 0.001). The five-year OS among women with HER2-positive ILC was 93.1%, 90.8%,and 78.8% in TNM stages I, II, and III respectively. In multivariate analysis, a significant difference in difference in overall survival was not observed between women with HER2 positive ILC and IDC (Hazard Ratio [HR]: 1.0, 95% Confidence Interval [CI]: 0.9 - 1.1, p=0.55). Among women receiving neoadjuvant chemotherapy, a complete pathological response was observed in 31.7% of women with HER2-positive ILC and 42.7% of HER2-positive IDC. In multivariate analysis, there was no difference in odds of achieving a complete pathological response to neoadjuvant chemotherapy between HER2-positive ILC and IDC (Odds Ratio [OR]: 0.8, 95%CI: 0.7 - 1.0, p=0.12). Higher odds of complete pathological response in HER2-positive ILC were observed for women with estrogen-receptor negative (OR: 2.0, 95% CI: 1.1- 3.8), p= 0.02) and progesterone-receptor negative (OR 2.4, 95%CI: 1.5- 3.7), p&lt; 0.001) tumors. The five-year OS for women with a complete pathological response, partial response, and no response after neoadjuvant chemotherapy in HER2-positive ILC were 89.6%, 84.9%, and 77.3% respectively (p=0.01). Conclusion: This study demonstrates that HER2-positive ILC has comparable clinical outcomes to HER2-positive IDC and response to neoadjuvant chemotherapy correlates with OS in HER2-positive ILC. These findings lend support to the current practice of treating HER2-positive ILC and IDC in a similar manner. Citation Format: Suman Gaire, Pravash Budhathoki, Utsav Joshi, Anish Shah, Grace M. Choong, Siddhartha Yadav. Clinical outcomes of loco-regional HER2-positive invasive lobular carcinoma of the breast [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-04.

Abstract Background: - Low levels of HER2 expression among women with HER2-negative breast cancer is an emerging target. In addition, prior studies have suggested that low levels of HER2 expression might confer resistance to chemotherapy among women with triple-negative breast cancer (TNBC). In this study, we assess the response to neoadjuvant chemotherapy among women with TNBC with varying degrees of HER2 expression. Methodology: - Utilizing the National Cancer Database, we identified adult women treated with neoadjuvant chemotherapy for a diagnosis of clinical TNM stage I to III triple-negative invasive ductal carcinoma of the breast between the years 2010 and 2018. Baseline characteristics were compared between HER2 immunohistochemistry (IHC) scores of 0, 1 +, and 2+ (Women with HER2 2+ expression had to be negative for amplification in the HER2 gene by FISH) using Chi-square for categorical variables. The odds of achieving a complete pathological response were compared among women with different HER2 expression statuses in a multivariate logistic regression model adjusting for age, race, ethnicity, grade of the tumor, and clinical TNM stage at diagnosis. A multivariate cox proportional hazards regression model was used to identify the prognostic effect of HER2 expression on overall survival (OS) adjusting for age at diagnosis, race, ethnicity, grade of tumor, and clinical TNM stage at diagnosis. Results: - A total of 11,038 women with HER2 IHC score of 0, 8,718 women with a score of 1+ and 2,700 women with a score of 2+ were included in the final analysis. The median age at diagnosis was 52 for women with a HER2 IHC score of 0, 53 for women with a HER2 IHC score of 1+ and 54 for women with an IHC score of 2+/FISH negative. The rates of complete pathological response among women with HER2 IHC scores of 0, 1+, and 2+ were 39.5%, 38.1%, and 36.1% respectively. In multivariate analysis, a significant difference in the odds of achieving complete pathological response was not observed for women with HER2 1+ (OR: 1.1, 95% CI: 0.95-1.20, p = 0.3) or HER2 2+ (OR: 0.9, 95% CI: 0.7-1.0, p = 0.1) tumors compared to women with HER2 IHC score of 0. In multivariate Cox regression analysis, women with TNBC with HER2 IHC score 2+ were found to have a better OS (Hazard Ratio [HR]: 0.88, 95% CI: 0.80-0.97, p = 0.01) compared to women with HER2 IHC score of 0 whereas a significant difference in OS was not observed between women with HER2 IHC scores of 0 and 1+ (HR: 0.95, 95% CI: 0.89–1.01, p = 0.1). Conclusion: - This study demonstrates that HER2 expression status does not influence the rates of complete pathological response to neoadjuvant chemotherapy in women with TNBC. However, women with HER2 IHC score of 2+ were found to have a favorable prognosis, which needs to be evaluated further in future studies. Citation Format: Pravash Budhathoki, Anish Shah, Suman Gaire, Utsav Joshi, Siddhartha Yadav. Response to neoadjuvant chemotherapy among women with triple-negative breast cancer by HER2 expression status [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-05.