Li, Shenduo

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.

e21030 Background: Docetaxel +/- ramucirumab remains the standard of care therapy after progression on platinum doublet and immune checkpoint blockade (ICB) in patients with metastatic non-small cell lung cancer (NSCLC). However, the clinical benefit from docetaxel is short-lived with substantial toxicity. Additionally, whether cancer gene mutation status impacts the benefit from docetaxel has not been systemically studied. In this real-world study, we aim to investigate whether cancer gene mutation status is associated with benefit from docetaxel. We also explored whether IMPOWER150-based regimens (ABCP-atezolizumab + bevacizumab + carboplatin + paclitaxel; ACP-atezolizumab + carboplatin + paclitaxel; BCP-bevacizumab + carboplatin+paclitaxel) may serve as alternative options with better efficacy in this patient population. Methods: We retrospectively queried MD Anderson Cancer Center GEMINI database for patients with metastatic NSCLC who received docetaxel, docetaxel+ramucirumab, or one of the above-mentioned IMPOWER150-based regimens after progression on concomitant or sequential platinum-doublet and ICI. Primary endpoints include progression-free survival (PFS) and overall survival (OS). Results: 274 patients were analyzed (docetaxel n = 99; docetaxel +ramucirumab n = 142; ABCP n = 28; BCP n = 4, ACP n = 1). No significant difference was observed in mPFS (3.00m versus 3.93m, P = 0.156) or mOS (8.40m vs.8.67m, P = 0.737) between patients from docetaxel monotherapy group and docetaxel+ ramucirumab group. Cancer gene mutations in EGFR, KRAS, TP53 or PD-L1 expression (0-1%; 1-49%; ≥50%) were not associated with PFS or OS in the 241 patients treated with docetaxel +/- ramucirumab. Furthermore, there was no difference in mPFS (5.50m versus 3.47m, P = 0.516) or mOS (10.40m versus 8.83m, P = 0.737) in patients who received IMPOWER 150-based regimens compared to those who were treated with docetaxel+/- ramucirumab. The median treatment duration was 1.60m (0.70m-20.23m), 1.90m (0.70m-32.90m), 4.80m(0.70m-33.47m) and 11 patients (11.11%), 20 patients (14.08%), and 3 patients (9.09%) discontinued treatment due to adverse events in the patients treated with docetaxel monotherapy, docetaxel+ramucirumab combined therapy, and the IMPOWER150 regimens, respectively. Conclusions: These results from this real-world study suggested that unlike for ICI therapy, where onco-driver mutations have profound impact on the clinical benefit, the cancer gene mutation status does not impact the benefit from docetaxel +/- ramucirumab in NSCLC patients who progressed on platinum doublets and ICI. Furthermore, the clinical benefit from docetaxel +/- ramucirumab is short-lived. Novel treatment regimens are urgently needed in this clinical setting.

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]

Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type and is still incurable for most patients at the advanced stage. Targeted therapy is an effective treatment that has significantly improved survival in NSCLC patients with actionable mutations. However, therapy resistance occurs widely among patients leading to disease progression. In addition, many oncogenic driver mutations in NSCLC still lack targeted agents. New drugs are being developed and tested in clinical trials to overcome these challenges. This review aims to summarize emerging targeted therapy that have been conducted or initiated through first-in-human clinical trials in the past year.

e21131 Background: Solid organ transplant recipients have increased risk for malignancies. Lung cancer is the second most common malignancy in this population. Those patients are usually on long-term immunosuppressive medications that may affect tumorigenesis, cancer characteristics, and treatment response. Previous studies have investigated the characteristics and outcomes of post-transplant patients with lung cancer in small-sized cohorts. However, the tumor mutational profile and detailed treatment response at different stages have not been reported. Methods: We conducted a retrospective study from a cohort of 52 solid organ transplant recipients who were diagnosed with lung cancer at Mayo Clinic from 2018 to 2021. We examined tumor molecular alteration using next generation sequencing (NGS), analyzed the treatment modalities, progression-free survival (PFS), and overall survival (OS) and compared those to the general population with lung cancer using historical data in previous large trials. Results: In our study, most transplanted solid organs are kidney (N = 28, 53.8%), followed by liver (N = 12, 23.1%) and heart (N = 9, 17.3%). The adenocarcinoma (N = 28, 53.8%) represented the most common histology, followed by squamous cell carcinoma (N = 19, 36.5%). It consisted of Stage I (30.8%), stage II (15.4%), stage III (25%), and stage IV (26.9%). The most common site of metastasis is bone (64.3%). Transplant recipients with lung cancer have a significantly high frequency of somatic BRCA 1/2 mutations (30.4%), compared to the general population with advanced lung cancer (2.1%, p < 0.001). The frequencies of TP53 mutations (52.2%) and EGFR mutations (30.4%) are also increased. For stage I patients who received surgery or radiation therapy, the disease-free survival (DFS) is 16.5 months. 9 of 14 stage IV patients received chemotherapy. The median number of cycles received is 4. The median PFS is 4.9 months, and the median OS of all stage IV patients is 6.1 months. 4 patients were found to have actionable EGFR mutations, and 3 of them were initially diagnosed with stage IIIA and received Osimertinib after progression. One stage IV patient who was post-liver transplant received pembrolizumab for up to 5 cycles before he developed aspiration pneumonia and then pursued hospice. The PFS is 3.7 months. No immune-related adverse event was reported. Conclusions: In our cohort of solid organ transplant recipients who developed lung cancer, we observed a much higher frequency of somatic BRCA 1/2 mutations, compared to the general population with lung cancer. In addition, our data suggested post-transplant patients with stage I lung cancer have a shorter disease-free survival, and patients with stage IV lung cancer have a shorter overall survival, compared to the general population with lung cancer. Further study containing a high number of solid transplant patients to validate these findings is warranted.