Inampudi, Jyothik Varun

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.

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.