Efficacy and outcomes of ramucirumab and docetaxel in patients with metastatic non-small cell lung cancer after disease progression on immune checkpoint inhibitor therapy: Results of a monocentric, retrospective analysis

Current first-line standard therapy for metastatic non-small cell lung cancer without driver mutations involves chemotherapy and immunotherapy combination. Prior to the advent of immune checkpoint inhibition, REVEL, a randomized phase III trial demonstrated improved progression-free and overall survival with ramucirumab and docetaxel (ram+doc) in patients who failed platinum-based first-line therapy. Long-term outcomes related to second-line ramucirumab and docetaxel after first-line immunotherapy exposure remain unknown. We analyzed outcomes for 35 patients from our center whom received ramucirumab and docetaxel following disease progression on chemotherapy and immunotherapy combination. Median progression-free survival among patients who received ram+doc after exposure to immunotherapy was 6.6 months (95% CI = 5.5 to 14.9 months; p<0.0001), and median overall survival was 20.9 months (95% CI = 13.4 months to infinity; p<0.0001). These outcomes suggest that there may a synergistic benefit to combining chemotherapy with anti-angiogenic therapy after immunotherapy exposure. Future analyses should be evaluated prospectively and among a larger patient subset

Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer

AbstractMETex14 skipping mutations occur in about 3–4% of lung adenocarcinoma patients and 1–2% of patients with other lung cancer histology. The MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are established oncogenic drivers of NSCLC. A mutation that results in loss of exon 14 in the MET gene leads to dysregulation and inappropriate signaling that is associated with increased responsiveness to MET TKIs. Results from GEOMETRY mono-1 and VISION Phase I/II clinical trials demonstrated significant clinical activity in patients treated with the MET Exon 14 skipping mutation inhibitors capmatinib and tepotinib with tolerable toxicity profile. In the GEOMETRY mono-1 trial, capmatinib was especially active in treatment-naïve patients supporting the upfront testing of this oncogenic driver. Tepotinib demonstrated superior activity in the pretreated patients in the VISION trial. Savolitinib is another MET TKI that has shown efficacy in the first- and second-line settings, including patients with aggressive pulmonary sarcomatoid carcinoma. These studies have demonstrated that these TKIs can cross the blood brain barrier and demonstrated some activity toward CNS metastases. MET Exon 14 skipping mutation is detected by NGS-based testing of liquid or tissue biopsies, with preference for RNA-based NGS. The activity of capmatinib and tepotinib is limited by the development of acquired resistance. Current research is focused on strategies to overcome resistance and improve the effectiveness of these agents. Our aim is to review the current status of MET Exon 14 skipping mutation as it pertains NSCLC

Therapeutic strategies in RET gene rearranged non-small cell lung cancer

The recent approvals by the Food and Drug Administration several tumor-agnostic drugs have resulted in a paradigm shift in cancer treatment from an organ/histology-specific strategy to biomarker-guided approaches. RET gene fusions are oncogenic drivers in multiple tumor types and are known to occur in 1-2% of non-squamous NSCLC patients. RET gene fusions give rise to chimeric, cytosolic proteins with constitutively active RET kinase domain. Standard therapeutic regimens provide limited benefit for NSCLC patients with RET fusion-positive tumors, and the outcomes with immunotherapy in the these patients are generally poor. Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are potent and selective inhibitors that target RET alterations, including fusions and mutations, irrespective of the tissue of origin. Recently, the results from the LIBRETTO-001 and ARROW clinical trials demonstrated significant clinical benefits with selpercatinib and pralsetinib respectively, in NSCLC patients with RET gene fusions, with tolerable toxicity profiles. These studies also demonstrated that these RET-TKIs crossed the blood brain barrier with significant activity. As has been observed with other TKIs, the emergence of acquired resistance may limit long-term efficacy of these agents. Therefore, understanding the mechanisms of resistance is necessary for the development of strategies to overcome them

Abstract A106: Disparities in the presence of driver mutations and response to tyrosine kinase inhibitors in young patients with lung cancer

Abstract Background: A concerning number of young patients (<50 years old) have been diagnosed with advanced lung cancer in recent years, likely due to driver mutations. This study examined disparities in the presence of driver mutations and response to tyrosine kinase inhibitors (TKI) in young patients with lung adenocarcinoma. Methods: This retrospective study included 98 patients (18-50 years old) with lung adenocarcinoma treated at the University of Miami Sylvester Comprehensive Cancer Center (2004-2023). Data from 81 patients with genetic information were analyzed. Patient demographics, clinical characteristics, and outcomes were collected. Chi- square and Kaplan-Meier methods were used, and p-values < 0.05 were considered significant. Results: Among the 17 patients without biomarker testing, 88% were white, 64.7% female and 59% Hispanic. The mean age at diagnosis for the 81 patients with genetic data was 41. Most were never smokers (56%), female (67%), white (83%), and Hispanic (52%) with stage IV disease (64%). At data cutoff in June 2023, 43 (53%) patients were alive, with a mOS of 27 months. Of the 81 patients, 58 (71.6%) had at least one driver mutation. The most common mutations were EGFR (31%), ALK (27%), and ROS1 (6%). No differences in mutation expression were found by gender, race, or ethnicity. Among patients with an actionable mutation, there were no significant differences in treatment with a TKI by race (p=0.337), gender (p=0.347), or ethnicity (p=0.940). However, 50% of eligible Black patients were not treated with a TKI compared to 26% of white patients. TKI as first-line treatment did not significantly vary by race (p=0.551), gender (p=0.883), or ethnicity (p=0.062), but 53% of white patients received a TKI as first-line therapy compared to 33% of Black patients. At data cutoff, there were no differences in the number of patients still taking a TKI based on gender (p=0.616), race (p=0.665), or ethnicity (p=0.465), although 46% of Hispanic patients were still on treatment compared to 35% of non-Hispanic patients. PFS on a TKI was similar for race (p=0.352) and gender (p=0.258), however Hispanic patients with an actionable mutation had a significantly longer PFS on a TKI than non-Hispanic patients (p=0.019), but not after controlling for age (p=0.116). Conclusion: This study is among the first to analyze disparities in driver mutations and response to targeted therapy in young patients with lung adenocarcinoma. No significant differences were found in TKI treatment, TKI as first-line therapy, or current TKI use by gender, race, or ethnicity. Notable trends included a greater percentage of eligible Black patients not receiving TKIs and fewer Black patients receiving TKIs as first-line therapy, although the sample of Black patients was small. Hispanic patients had a significantly longer PFS on TKIs than non-Hispanics, but not after controlling for age. Further research is needed to evaluate these trends, particularly with a larger cohort of Black patients. Citation Format: Kyle Edwards, Brandon Rose, Gilberto Lopes, Estelamari Rodriguez, Coral Olazagasti. Disparities in the presence of driver mutations and response to tyrosine kinase inhibitors in young patients with lung cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A106

Using social media and direct marketing as a platform to increase awareness of lung cancer screening in a Hispanic urban population in the post-COVID period

339 Background: Uptake in lung cancer screening (LCS) in high-risk patients including minority populations has been low despite efforts to increase awareness in the community. During the COVID pandemic, most LCS programs were temporarily stopped and, in the months to follow experienced a significant reduction in referrals. Platforms including social media and direct mail marketing can provide a valuable tool to enhance patient engagement related to LCS and engagement of Hispanic populations who are active consumers of digital media. The objective of this study was to assess the short-term effectiveness of a targeted LCS digital and direct marketing campaign to increase visits to the institutional online educational content and referrals to a LCS program. Methods: A LCS marketing campaign including social media utilizing Facebook and Instagram platforms with programmatic banners, boosted organic social media posts, plus direct mail-in marketing in Spanish and English was started in the post-COVID period. A CRM (customer-relationship management) software was used to target adults ages 50-80, current or former smokers, who speak English and/or Spanish in the Miami tri-county area over a three-month period by a direct-mail campaign. Other campaign targeting qualifications included family history of lung cancer, and additional lung cancer risk factors including asbestos, chronic obstructive pulmonary disease, or emphysema. The CRM Direct mail campaign was sent 87,000 leads by postcard and 65,810 leads by email. Primary outcomes measures were visits to the University of Miami institutional LCS Web page, LDCT ambulatory referrals, and scheduled initial LDCT exams. Study period was baseline pre-COVID period (6/1/2019-12/31/2019), COVID-period (3/1/2020-9/31/2020) and digital awareness campaign in the post-COVID period (12/1/2020-5/31/2020). Results: Unique pageviews to the institutional LCS web pages were significantly higher during the digital awareness campaign compared to the pre-COVID period (8,805 vs 230 pageviews) with a high bounce rate during the campaign period of 79% and average time in site of 2:21 minutes. Mean scheduled initial LDCT volumes per month during the pre-COVID period were 12.4 (SD 4.6), versus 4.1 (SD 2.5) during the COVID period. There was a 3-fold increase in initial LDCT scans during the initial campaign period from 4.1 in the COVID period to 11.6 (p <.001). The mean number of LDCT ambulatory referrals doubled from 17.5 in the COVID period to 34.2 in the campaign period (p < 0.001). Conclusions: Implementation of a targeted LCS digital awareness campaign and direct mail marketing was associated with increased visits to institutional education Web pages, ambulatory referrals, and initial LDCT exams. Digital platforms are an important tool to enhance awareness of lung cancer screening in high-risk populations and Hispanics

Disparities in Electronic Cigarette Use: A Narrative Review

The prevalence of electronic cigarette use has been declared an epidemic by the U.S. Surgeon General in 2018, particularly among youth aged 18−24 years old. Little is known about the differential use of e-cigarettes by different groups. PubMed, Cochrane, and Google Scholar were used to find relevant articles. A total of 77 articles were included. The extant literature reveals disparities in e-cigarette use by race/ethnicity and sexuality/gender. There are conflicting conclusions regarding disparities by socioeconomic status

Abstract B040: Understanding disparities in clinical trial enrollment: A study of screen failures to phase I clinical trials in a minority-serving institution in the post-COVID period

Abstract Background: Phase 1 clinical trials offer a novel therapeutic option to individuals who have progressed past standard of care treatment and valuable data oncological field advancement. Previous research has shown that a significant proportion of patients referred for clinical trials do not meet eligibility criteria and are considered screen failure (SF) after consenting and even more patients referred are pre-screen failure before consenting (PSF). In addition, historically, the rate of clinical trial enrollment has been low in underrepresented minorities. These SF rates and disparities could have further increased due to COVID challenges. In this study, we aim to define the most common reasons for SF and study disparities in trial enrollment demographics in the post-COVID period.  Methods: A cross-sectional sample of patients referred to the Sylvester Comprehensive Cancer Center Phase I Clinic during the pre-COVID period (11/2018-12/2019) and post-COVID period (11/2021-12/2022) was analyzed. Patients’ demographics, malignancies and SF patterns were analyzed. Reasons for SF were categorized as: cancer progression, clinical trial ineligibility, lack of applicable trial, system delays due to staffing, patient hesitancy/refusal or loss to follow-up. Chi square tests were then used to analyze the SF rate based on patient demographics.  Results: During the pre-COVID period, 98 patients consented and 75 enrolled with a screen failure of 21.4%, compared to the post-COVID period when 101 patients consented and 74 enrolled with a screen failure of 27.7%.  During the post-COVID period, 69 patients were PSFs, and 4 patients waitlisted and never consented. Of the PSF (n=69), 37 (55%) were female, 27 (40%) were Hispanic, 10 (15%) were Black, and 1 (1%) was Asian. The majority of PSFs were patients with thoracic cancer (45.5%), followed by GI (19%) and GYN malignancies (16.1%). The main reasons endorsed for PSFs were patients refusal/loss to follow up (35%), not consented due to system delays (20.5%), cancer progression (20.5%), trial ineligibility (17%), and lack of applicable trial (7%). When using chi square tests to analyze the prescreen failure vs. enrollment rate based on patient demographics, there was no statistically significant difference between race (p=0.19), ethnicity (p=0.45), or gender (p=0.22).  Conclusion: Though the number of patients enrolled in the pre- and post-COVID period was similar, the rate of screen and prescreen failures differed.  Trial design ineligibility, patient hesitancy/loss to follow up, and systemic challenges due to staff shortages contributed to SFs in the post COVID period.  Staff shortages after the COVID-19 pandemic affected Phase 1 trial enrollment but was not the predominant SF reason.  Studies to address clinical trial complexity and issues of patient hesitancy and withdrawal from clinical trial process are needed.  The lack of demographic disparities in enrollment and SFs suggest that these system issues did not disproportionately affect any demographic group in this diverse cohort. Citation Format: Sapna A. Kedia, Rakhi Modak, Nora A. El-Abbar, Jaime R. Merchan, Estelamari Rodriguez. Understanding disparities in clinical trial enrollment: A study of screen failures to phase I clinical trials in a minority-serving institution in the post-COVID period [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B040

Abstract 1949: KRAS G12C mutations in Hispanic and non-Hispanic patients with NSCLC: clinicopathologic characteristics and prognosis

Abstract Background: KRAS mutations, which are associated with tobacco use, have been linked to worse survival in patients with non-small cell lung cancer (NSCLC). KRAS G12C is the most frequent actionable mutation detected in NSCLC, with a prevalence of 13%. The incidence of KRAS G12C mutations and potential impact on treatment response for Hispanic patients with lung cancer has not been well characterized. Methods: A total of 110 patients (77 non-Hispanic [NH] and 33 Hispanic) with a diagnosis of NSCLC and next generation sequencing information available treated at the University of Miami from 2013-2021 were included. Incidence of KRAS G12C mutations, clinicopathologic characteristics, treatment response and overall survival were analyzed. Results: The prevalence of the KRAS G12C mutation was 7.6% in the whole cohort. The prevalence of KRAS G12C co-mutations in NH vs Hispanic was 9.3% vs 5.7%. Median age of NH vs Hispanic patients was 69.5 yrs vs 66.4 yrs. (Table 1) In both the NH and Hispanic cohorts, there were more women (56% vs 51.5%), as well as smokers (97% vs 97%). In both cohorts, most patients had non-squamous histology (94%). In the NH cohort, the majority were PDL1 negative (50%). In the Hispanic cohort, there was a more even distribution of PDL1 expression status: negative (30%), low (33%), and high (24%). Median DOR for chemotherapy in NH vs Hispanics was 16 mos vs 14 mos (p=0.77). Median DOR for immunotherapy in NH vs Hispanics was 18 mos vs 12 mos (p=0.30). Median OS in NH vs Hispanics was 36 mos vs 29 mos (p=0.25). Conclusion: There was no statistical difference in prevalence of KRAS G12C mutations between NH and Hispanics. Notably, both cohorts had a significant smoking history. KRAS G12C portends equally poor prognosis and treatment resistance as evidenced by median DOR and OS for both Hispanics and NH patients. However, Hispanic patients demonstrated a trend of decreased OS and DOR to IO compared to NH patients. Clinicopathologic characteristics and prognosis of NH and Hispanic Patients with KRAS G12C mutation `Characteristic Non-Hispanic (n = 77) Hispanic (n =33 ) P Value Total Patients (%) 77 (70%) 33 (30%) Status 37(48%) 14(42%) Alive(%) 40(52%) 19(58%) Deceased(%) Median Age (Years [Range]) 69.5 (47-92) 66.4 (41-84) 0.13 Gender 34(44%) 17(52%) Male(%) 43(56%) 16(48%) Female(%) Race 70(91%) 32(97%) White(%) 4(5%) 1(3%) African American(%) 1(1%) 0(0%) Asian (%) 2(3%) 0(0%) Other(%) Tobacco Use 2(3%) 1(3%) Never(%)1 Pack/Day(%) Histology 73(94%) 31(94%) Non-squamous(%) 2(3%) 0(0%) Squamous(%) 2(3%) 2(6%) Mixed/Other(%) PD-L1 Status 39(50%) 10(30%) Negative(%) 13(17%) 11(33%) Low expression(50%)(%) 12(16%) 4(13%) Unknown(%) Stage 1(1%) 1(3%) IA(%) 5(6%) 2(6%) IB(%) 3(4%) 0(0%) IIA(%) 4(5%) 3(9%) IIB(%) 11(15%) 4(12%) IIIA(%) 4(5%) 0(0%) IIIB(%) 46(60%) 22(67%) IV(%) 3(4%) 1(3%) Unknown(%) Metastases* 487(12%) 265(17%) Any metastasis/multiple sites 2(4%) 0(0%) Lung 5(9%) 3(11%) Liver 13(22%) 7(25%) Adrenal 18(31%) 9(33%) Bone 13(22%) 4(14%) Brain Other Chemotherapy 20(26%) 10(31%) No Chemotherapy(%) 28(36%) 12(36%) Platinum + Pemetrexed(%) 6(8%) 1(3%) Platinum + Taxane(%) 4(5%) 8(24%) Chemotherapy + Immunotherapy(%) 9(12%) 1(3%) Single Agent Chemotherapy(%) 10(13%) 1(3%) Unknown(%) Median duration of response to chemotherapy 14 months 16 months 0.77 Immunotherapy 27(35%) 18(54%) Yes(%) 40(52%) 13(40%) No(%) 10(13%) 2(6%) Unknown(%) Median duration of response to immunotherapy 18 months 12 months 0.30 Median Survival Time 36 months 29 months 0.25 Median Survival Time in Stage IV Patients 29 months 20 months 0.92 *Percentages may not equal 100 Citation Format: Aysswarya Manoharan, Samuel A. Kareff, Leana M. Ramos, Nora A. El-Abbar, Gilberto Lopes, Estelamari Rodriguez. KRAS G12C mutations in Hispanic and non-Hispanic patients with NSCLC: clinicopathologic characteristics and prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1949