Manochakian, Rami

Abstract Background Immune checkpoint inhibitor combined with platinum‐etoposide is the standard first‐line therapy for patients with extensive‐stage small cell lung cancer (ES‐SCLC). The phase 3 clinical trials that led to the approval of chemoimmunotherapy in ES‐SCLC excluded patients who had an Eastern Cooperative Group (ECOG) performance status (PS) of 2–3. Therefore, data on the efficacy of chemoimmunotherapy in patients with an ECOG PS of 2–3 are limited. Methods A retrospective analysis was performed on patients diagnosed with ES‐SCLC who received chemoimmunotherapy (atezolizumab or durvalumab) within the Mayo Clinic Health System between January 2016 and January 2021. The objective of this study was to compare the overall survival (OS), progression‐free survival (PFS), and best clinical response to therapy in patients with an ECOG PS of 0–1 vs. patients with an ECOG PS of 2–3 who received chemoimmunotherapy for newly diagnosed ES‐SCLC. Results In total, 82 patients were included in the study. The mean ± standard deviation age was 68.1 ± 8.3 years. Of these, 56 patients were identified with an ECOG PS of 0–1, and 26 patients were identified with an ECOG PS of 2–3. The median PFS was similar regardless of ECOG PS (5.8 months [95% CI, 4.3–6.0 months] in the ECOG PS 0–1 group vs. 4.1 months [95% CI, 3.8–6.9 months] in the ECOG PS 2–3; p = .2994). The median OS was also similar regardless of ECOG PS (10.6 months [95% CI, 8.4–13.4 months] in the ECOG PS 0–1 group vs. 9.3 months [95% CI, 4.9–12.8 months]; p = .2718) in the ECOG PS 2‐3 group. Conclusions The study results demonstrated no significant difference in PFS or OS among the ECOG PS 2–3 and ECOG PS 0–1 groups. Therefore, chemoimmunotherapy should be considered for patients who have ES‐SCLC with an ECOG PS of 2–3.

AbstractBackgroundClinical trials are an essential part of advancing care for cancer patients. Historically, however, racial minorities and females have been underrepresented in these trials. Efforts like the National Institute of Health Revitalization Act attempted to mitigate these disparities, but despite these efforts, they continue to exist. These disparities can subsequently lead to minorities and females receiving suboptimal care.AimsThe purpose of our study was to understand the changing trends in reporting of participant race and sex as a demographic variable in phase III lung cancer clinical trials published over the last 35 years given these consequences of poor representation.Methods and resultsA total of 426 articles reporting the results of phase III lung cancer clinical trials published from 1984 to 2019 were identified in PubMed. From these articles, data on participant sex and race were collected from the demographic tables to construct the database for this study. This database was subsequently used to determine the rate of reporting of demographic factors like race and sex and the participation trends over the time of minority and female participation in lung cancer phase III clinical trials. The SciPy Stats package for Python was used to calculate descriptive statistics, 95% confidence intervals, two sample t‐test, one‐way analysis of variance test, and Pearson's correlation coefficients. The Matplotlib package for Python was used for figure generation. Only 137 (32.2%) of the 426 studies analyzed reported the race of participants. Among those studies, we found that the mean participation rate of White participants was significantly higher (82.65%; p < .001). We found a decrease in African American participants and an increase in Asian participants over time. When looking at sex, we found that although the rate of male participation (69.02%) was significantly higher than that of female participation (30.98%), female participation has improved with time at a rate of 0.65% per year.ConclusionWe found that the reporting and participation of minority races continue to lag that of other demographic factors like sex in phase III clinical trials in lung cancer. Based on our analysis, we note a decline in participation of African Americans in lung cancer phase III clinical trials despite the rising incidence of lung cancer.

12051 Background: The combination of ipilimumab and nivolumab (Ipi-Nivo) is a standard of care regimen in many malignancies. However, immune-related adverse events (irAE) are common and are of great concern, especially when treating the elderly population. This subgroup of patients may be at greater risk for serious irAEs and be less able to tolerate the potential treatment side effects. We sought to retrospectively evaluate our experience treating elderly patients ≥ 80 years with Ipi-Nivo to characterize adverse events. Methods: A retrospective chart review of the electronic medical records of all patients treated with Ipi-Nivo at the Mayo Clinic Health System was performed. Patients with any solid tumor who received their first dose of Ipi-Nivo at the age of ≥ 80 were included. Records were analyzed for baseline characteristics, cancer type, toxicity, and response to therapy. Differences between continuous and categorical variables were assessed using the students’ t-test and the chi-squared test, respectively. Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazard models assessed the relative contribution of factors to survival after treatment. P values < 0.05 were considered statistically significant. All analyses were performed using SAS V.9.4. Results: Forty-six patients met inclusion criteria, 13 females and 33 males. Median age of first dose was 83 (Range: 80 - 94). Sixty-seven percent had an ECOG performance status (PS) 0-1 and 33% had an ECOG PS 2-3. Thirteen (28.3%) patients received 4 cycles of Ipi-Nivo. Cancers included: 18 (40%) melanomas, 10 (21%) mesothelioma, 9 (19.5%) lung cancers, and 9 (19.5%) other types. Thirty-one patients (67%) developed at least one irAE. Of the irAEs, 8 (17.4%) were grade 1, 20 (43.5%) were grade 2, 14 (30.4%) were grade 3, and 3 (6.5%) were grade 4. Systemic steroids were used in 29 (63%) patients. Twenty-six (56.5%) patients were hospitalized for any cause, and 12 (26.1%) were hospitalized due to an irAE. Of the 26 patients hospitalized during treatment, 19 (73%) died within 1 year of discharge; 11 (42%) died within < 1 month of discharge and 3 (12%) died within 1-3 months of discharge. Median OS from the date of first Ipi-Nivo dose was 14.6 months in the ECOG PS 0-1 and 6.5 months in the ECOG PS 2-3. ECOG PS of 0-1 was associated with a significantly decreased risk of mortality (HR [hazard ratio] 0.33, 95 % CI [confidence interval]: 0.15-0.70; p=0.0025) compared to ECOG PS of 2-3. Conclusions: This is the first analysis to evaluate the outcomes of Ipi-Nivo in patients ≥ 80 years. Approximately 60% of the patients required systemic steroids and a quarter were hospitalized with grade 3-4 irAEs. As expected, patients with ECOG PS 2-3 did significantly worse than ECOG PS 0-1. Ipi-Nivo should be used with caution in patients ≥ 80 years.

e21161 Background: Patients with stage IV NSCLC undergo frequent restaging scans (RS). While vital to assess treatment response, RS add anxiety and financial burdens to patients. The ideal frequency of RS is unclear. The numerous treatment options available, such as targeted therapy (TT) and immunotherapy (IO), and the variability in frequency of RS in the trials that led to their approval reflect this uncertainty. Due to the lack of clear guidelines about their ideal interval in daily practice, we reviewed the heterogeneity in frequency of RS in those trials, comparing it to the reported progression-free survival (PFS). Methods: In this study, we reviewed the FDA-approved drugs for stage IV NSCLC since 10/18/2016 and selected the TT and IO. Each trial that led to approval was reviewed, collecting the frequency of RS and the median PFS for the intervention (IA) and control arms (CA). Results: 18 TT drugs and 12 IO regimens, with and without chemotherapy (chemo), were found. Among them, the frequency of RS varied from every 4 to 9 weeks (w) upfront, later modified to every 6 to 12 w until disease progression. The median PFS for both groups in the IA ranged from 2.8 to 19.4 months (m), and from 3.0 to 12.4 m in the CA. The TT group had drugs directed at 7 different mutations, and it presented more discrepancy in terms of restaging frequency. The period between RS varied from every 4 to 8 w initially, later modified to every 6 to 12 w. However, 11 of 18 trials had an interval of every 6 w. The shortest median PFS in the IA arm was 5.4 m, and 5.6 m in the CA. While the longest median PFS was 19.4 m in the IA and 12.4 m in the CA. The IO group included 5 regimens with chemo and 7 without. The interval between RS varied from 6 to 9 w originally, to every 8 to 12 w later. Yet, 8 of 12 regimens’ trials scanned patients every 6 w initially. The median PFS in the IA ranged from 2.8 to 10.3 m, and between 3.0 to 6.5 m in the CA. Conclusions: We observed notable heterogeneity among trials regarding the frequency of RS in patients treated for stage IV NSCLC. When comparing these intervals to the median PFS, we noted the shortest PFS reported is longer than most adopted intervals. This may indicate RS were obtained more frequently than needed. The increased frequency of RS raises a burden for patients and the medical system, while contributing to disparities. This finding, coupled with further comparisons between the frequency of RS in trials and in daily practice, may pave the way for prospective studies analyzing the ideal interval for RS. This can lead to a more efficacious and less burdensome strategy for patients. [Table: see text]

e21157 Background: Atezolizumab is superior to docetaxel for patients with advanced non-small-cell lung cancer (NSCLC) who are pretreated with platinum-based chemotherapy based on the POPLAR and OAK trials. However, patients who received prior immunotherapy (IO) were excluded from these trials. The preferred subsequent therapy for these patients remains to be docetaxel +/- ramucirumab. The efficacy and safety of atezolizumab as a subsequent therapy in IO-pretreated patients are unknown. Methods: We conducted a retrospective study of all patients with locally advanced/metastatic NSCLC who were pretreated with IO at Mayo Clinic Florida/Rochester in 2016 - 2022. Patients who received subsequent therapy of atezolizumab alone (Atezo), docetaxel (Doce), or docetaxel + ramucirumab (Doce+Ram) were included. Kaplan-Meier method and log-rank test were used for survival analysis. Results: Among 169 patients included, 51.5% were female, 91.7% were Caucasian. The median age was 67 (35 – 92). The histology was predominantly adenocarcinoma (76.3%). The most common metastatic sites were bone (51.5%), followed by CNS (44.4%). The median number of prior therapies was 2 (1 – 8). Pembrolizumab was the most used prior IO (87%), followed by durvalumab (10.7%) and nivolumab (8.3%). 13.6% (n = 23), 49.1% (n = 83), and 37.2% (n = 63) patients received subsequent Atezo, Doce, and Doce+Ram, respectively. PFS was improved in the Atezo group compared with Doce group (median PFS 3.9 vs. 3.7 months, HR 0.57, 95% CI 0.37 – 0.87, p = 0.015*). Notably, a prominent percentage of patients in the Atezo group appear to have long-term PFS benefits, demonstrated by 1-year PFS rates of 26.1%, 3.6%, and 4.8% (p = 0.003**), and 2-year PFS rates of 17.4%, 0%, and 0% (p = 0.002**), in the Atezo, Doce, and Doce+Ram groups, respectively. The median OS (months) in the Atezo, Doce, and Doce+Ram groups were 17.5, 7.6, and 11.5, respectively; and were 29.5, 7.2, and 6.9, respectively in the PD-L1 > 50% subgroups. The Atezo group showed significantly greater OS improvement compared with the Doce group (HR 0.42, 95% CI 0.26 – 0.66, p = 0.001**). This benefit appears greater and remains statistically significant in the PD-L1 > 1% (HR 0.39, 95% CI 0.22 – 0.71, p = 0.005**) and PD-L1 > 50% (HR 0.37, 95% CI 0.15 – 0.91, p = 0.022*) subgroups. 5 of 23 (21.7%) patients in the Atezo group developed immune-related adverse events. 3 patients were grade 3 or 4. No grade 5 event. Conclusions: We observed statistically significant and clinically meaningful PFS and OS benefits of atezolizumab monotherapy compared with docetaxel in patients with advanced NSCLC who were pretreated with IO. The OS benefits of atezolizumab over docetaxel +/- ramucirumab was greater in PD-L1 > 1% and PD-L1 > 50% subgroups. Atezolizumab appears to be tolerable in IO-pretreated patients. These findings need to be verified in a prospective study.

e21156 Background: Immunotherapy (IO) is one of the major treatments for patients with metastatic non-small cell lung cancer (mNSCLC). IO may be discontinued in patients for many reasons, the most common being progression of disease (POD). For those patients who discontinued IO for reasons other than POD, such as immune-related adverse event (irAE), there is limited data that compare progression-free survival (PFS) and overall survival (OS) when IO is continued vs. stopped. Methods: We conducted a retrospective study of all patients with mNSCLC (stage IV) treated with IO at our institution from 2011 to 2022. Patients who discontinued IO due to POD were excluded from the analysis. The clinical outcomes, including PFS, OS, and irAE were investigated among patients with no POD who stopped IO prior to 6 or 12 months (m) vs. those that continued IO > 6 or 12m. Results: The analysis at the 6m timepoint included 92 patients, 82.6% were white, 50% were male, 67.4% had adenocarcinoma, and 82.6% used tobacco. The most common site of metastasis was bone (28.3%), followed by CNS (20.7%). 51.2% of patients had received IO as the first line systemic therapy and 32.6% received it as their second. Pembrolizumab was the most used IO (84.78%). Among these patients, 25 discontinued IO before 6m, and 67 patients continued IO beyond 6m. irAE, of any grade, occurred in 44.0% vs 37.3% when comparing IO discontinued with IO continued group at 6m. Patients who continued treatment beyond 6m had a longer duration of PFS (22.8m vs 11.8m, p = 1.14E-04) with a significant increase in OS (34.5m vs 14.0m, p = 1.34E-07). The analysis at the 12m timepoint included 71 patients, 87.3% were white, 46.5% were male, 78.9% had adenocarcinoma, and 80.3% used tobacco. The most common site of metastasis was bone (29.9%), followed by CNS (22.5%). 62.0% of patients had received IO as the first line systemic therapy and 28.7% received it as their second. Pembrolizumab was the most used IO (87.3%). Among these patients, 30 discontinued IO before 12m, and 41 patients continued IO beyond 12m. irAE, of any grade, occurred in 36.7% vs 41.5% when comparing IO discontinued with IO continued group at 12m. Similarly, patients who continued treatment beyond 12m had a longer duration of PFS (28.4m vs 14.2m, p = 1.91E-06) with a significant increase in OS (39.9m vs 17.6m, p = 3.45E-09). Conclusions: We observed that patients with mNSCLC and no POD, who continued IO beyond 6m and 12m, experienced a significant increase in PFS and OS than those who discontinued IO, with more significant increases in those who continued IO past 12m. These findings need to be verified in a larger cohort.

e20540 Background: Mesothelioma is an aggressive malignancy with few approved treatment options. Rare malignancies are often seen in higher volume at academic centers which are considered equipped with better expertise. Outcomes of mesothelioma in the novel therapeutic era and impact of initial treatment at academic versus community centers have not been reported. Methods: Mesothelioma cases from 2004-2019 were collected from The National Cancer Database (NCDB). Epidemiologic factors including sex, age, income, education, insurance status and location were assessed as well as overall survival across academic and community centers. Overall survival (OS) was plotted by type of treatment facility, accounting for several factors available in NCDB. Results: A total of 30136 mesothelioma patients were included in the analysis. 13482 (44.7%) were treated in academic centers and 16654 (55.3%) were treated in community practice locations. A higher proportion of patients with comorbidity scores of 2 or higher were seen in the community setting as compared to the academic setting (12.2% vs 7.6%). The distribution of diagnostic stages was similar between academic and community settings (14.1% vs 14.5% Stage I; 28.5% vs 30.7% Stage IV). A higher number of patients received surgery (39.6% vs 21.3%), chemotherapy (59% vs 45.3%), and immunotherapy (5.2% vs 3.5%) when presenting to academic rather than community settings, respectively (p value < 0.001). OS for all patients was 1.093 years (range: 0-16.47 years) for those treated in an academic center and 0.66 years (95% CI: 0-16.690; p < 0.001) for those treated in the community. Conclusions: Data from NCDB database shows that treatment of mesothelioma at academic centers was associated with improved overall survival when compared to receiving treatment in the community despite seeing similar proportions of early and late-stage disease at presentation. Patients were more likely to receive treatment of any kind if presenting to academic centers.

e20535 Background: Malignant peritoneal mesothelioma (MPM) is a rare disease with about 600 new cases per million people diagnosed annually in the U.S. High incidence of germline mutations has been reported in MPM patients (pts) without asbestos exposure. However, the incidence rate of developing multiple primary cancers in this population is unknown. The aim of this study is to investigate the frequency of additional malignancies in MPM pts. Methods: Using the Mayo Clinic Cancer Registry, we identified 64 pts who were treated for MPM from January 2002-December 2022 with updated follow-up data until 01/15/2023. Electronic medical records were reviewed. Results: Among the patient cohort, 25 pts were male, and 39 pts were female. 14/64 (22%) pts were found to have at least one additional malignancy, including breast cancer (4/14, 29%), colon cancer (3/14, 21%), lymphoma (3/14, 21%), ovarian cancer (2/14, 14%), melanoma (2/14, 14%), anal squamous cell carcinoma (1/14, 7%), papillary thyroid cancer (1/14, 7%), Chronic lymphocytic leukemia (1/14, 7%), renal cell carcinoma (1/14, 7%), squamous cell carcinoma of tongue (1/14, 7%), hepatocellular carcinoma (1/14, 7%) and pituitary macroadenoma (1/14, 7%). 4/14 (29%) pts had more than one (2-4) non-MPM malignancies. The median age at diagnosis of MPM was 65 years (44-82). The median age at diagnosis of non-MPM malignancies was 66 years (18-81). Most of the patients (11/14) were diagnosed with non-MPM malignancy within 12 months of diagnosis of MPM. Most pts (11/14, 78%) were diagnosed with non-MPM malignancy first, among which 5 pts (45%) were found to have MPM on surveillance scans. Germline mutation information was not available except for 2 pts with known family history (FH) of Lynch syndrome and Li-Fraumeni syndrome. FH was available in 29 pts, out of which 28 pts had FH of cancer identified in first-degree relatives. Among the 14 pts with additional malignancies, 9 pts had FH of cancer in first-degree relatives. Among all pts, 15 (18%) pts had a history of asbestos exposure. Among pts who also had non-MPM malignancies, 3/14 (21%) pts had a history of asbestos exposure. Among the 21 non-MPM cancers, 1/21 (5%), 11/21(52%), 1/21(5%), 3/21(14%), and 5/21(24%) non-MPM malignancies were stage 0, stage I, II, and III, or unknown at the diagnosis respectively. All except 1 pt underwent curative treatment for their non-MPM malignancies, and 12 pts had no evidence of disease at death or the time of last follow-up. Conclusions: The rate of multiple primary malignancies in pts with MPM is high, indicating possible genetic predisposition associated with this disease. Early genetic consultation and evaluation for germline mutations may need to be considered for these pts to improve long-term outcomes.

e18097 Background: Sorafenib and lenvatinib are FDA-approved MKIs for locally recurrent or metastatic, progressive, DTC refractory to radioactive iodine treatment. Cabozantinib showed a survival benefit in radioiodine-refractory DTC previously treated with sorafenib and/or lenvatinib and was granted FDA approval. Our study aims to investigate the benefit of other MKIs in DTC beyond the first-line setting. Methods: DTC patients (pts) treated with multiple lines of MKIs from August 2018 to July 2022 at Mayo Clinic across all sites were identified. Electronic medical records were reviewed. 6-month, 12-month, and 18-month progression-free survival (PFS) were calculated for all lines of therapy using RECIST 1.1 criteria. Results: Among the 9 pts identified, 4 were male. The median age was 65 years (43-75). Most pts (60%) had papillary thyroid cancer. All pts received lenvatinib as first line treatment. The 6, 12 and 18-month PFS were 89%, 89%, and 55% respectively. 6 pts discontinued lenvatinib due to progression of disease (PD). 3 pts discontinued it due to adverse effects (AEs), which included hemoptysis (1 pt), severe rash (1 pt) and multiple psychiatric manifestations (1 pt). 8 pts received pazopanib, and 1 patient received cabozantinib with ipilimumab (1 dose) and nivolumab (6 months - discontinued due to myocarditis) as second-line therapy. Among them, 1 patient received pembrolizumab plus everolimus for 2 months before receiving pazopanib. The 6, 12 and 18-month PFS were 55%, 22%, and 11% respectively. All pts ceased treatment due to eventual PD, and there were no toxicity-related discontinuations. 5 pts subsequently received third-line MKIs, including cabozantinib (3 pts), pazopanib (1 pt), and lenvatinib (1 pt). The pt who received lenvatinib had discontinued it as first line therapy due to toxicity. The 2 pts treated with third-line cabozantinib and the pt rechallenged with lenvatinib showed no PD at 12-months and no toxicity related discontinuation. Conclusions: Pazopanib was associated with durable PFS and good tolerability when offered after PD or intolerance on lenvatinib in this retrospective analysis, warranting a randomized prospective study. [Table: see text]

e16621 Background: Adrenocortical carcinoma (ACC) is an exceedingly rare aggressive endocrine malignancy with about 1 new case per million people diagnosed annually in the US. Higher incidence of ACC has been reported in patients (pts) with inherited syndromes such as Lynch syndrome and Li-Fraumeni syndrome. However, the incidence rate of developing multiple primary cancers in this population is unknown. The aim of this study is to investigate the frequency of additional malignancies in ACC patients. Methods: Using the Mayo Clinic Cancer Registry, we identified 63 pts who were treated for ACC from 2010- 2018 with updated follow up data until 01/31/2023. Electronic medical records were reviewed. Results: Among the patient cohort, 22 pts were male. 18/63 (29%) pts were found to have at least one additional malignancy, including basal cell carcinoma (3/18, 17%), melanoma (3/18, 17%), thyroid cancer (3/18, 17%), prostate cancer (3/18, 17%), squamous cell carcinoma of skin (2/18, 11%), renal cell carcinoma (2/18, 11%), breast cancer (2/18, 11%), leukemia (2/18, 11%), lung cancer (1/18, 6%), transitional cell malignant neoplasm of kidney (1/18, 6%), squamous cell carcinoma of tonsil (1/18, 6%), ovarian cancer (1/18, 6%), seminoma (1/18, 6%) and bladder cancer (1/18, 6%). 8/18 (45%) pts had more than one (2-3) non-ACC malignancies. The median age at diagnosis of ACC was 56 years (02-83). The median age at diagnosis of non-ACC malignancies was 54 years (25-72). Most of the patients (13/18) were diagnosed with non-ACC malignancy within 5 years of diagnosis of ACC. Most pts (13/18, 72%) were diagnosed with non-ACC malignancy first. Germline mutation information was not available except for 2 pts with known family history (FH) of Lynch syndrome and 2 pt with a known FH of Li-Fraumeni syndrome. FH was available in 38 pts, out of which 29 pts had FH of cancer identified in first-degree relatives. Among the 18 pts with additional malignancies, 12 pts had FH of cancer in first-degree relatives. All except 2 pts underwent curative treatment for their non-ACC malignancies, and 14 pts had no evidence of disease at death or the time of last follow-up. Conclusions: The rate of other multiple primary malignancies in pts with ACC is high, indicating possible genetic predisposition associated with this disease; Early genetic consultation and evaluation for known and novel germline mutations may need to be considered for these pts to improve long-term outcomes.