Adjuvant Therapy In Patients Research Articles

Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options.

The development of tyrosine kinase inhibitors (TKIs) targeting the mutant epidermal growth factor receptor (EGFR) protein initiated the success story of targeted therapies in non-small-cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently indicated as first-line therapy in patients with NSCLC with sensitizing EGFR mutations, as second-line therapy in patients who present the resistance-associated mutation T790M after treatment with previous EGFR-TKIs, and as adjuvant therapy for patients with early stage resected NSCLC, harboring EGFR mutations. Despite durable responses in patients with advanced NSCLC, resistance to osimertinib, similar to other targeted therapies, inevitably develops. Understanding the mechanisms of resistance, including both EGFR-dependent and -independent molecular pathways, as well as their therapeutic potential, represents an unmet need in thoracic oncology. Interestingly, differential resistance mechanisms develop when osimertinib is administered in a first-line versus second-line setting, indicating the importance of selection pressure and clonal evolution of tumor cells. Standard therapeutic approaches after progression to osimertinib include other targeted therapies, when a targetable genetic alteration is detected, and cytotoxic chemotherapy with or without antiangiogenic and immunotherapeutic agents. Deciphering the when and how to use immunotherapeutic agents in EGFR-positive NSCLC is a current challenge in clinical lung cancer research. Emerging treatment options after progression to osimertinib involve combinations of different therapeutic approaches and novel EGFR-TKI inhibitors. Research should also be focused on the standardization of liquid biopsies in order to facilitate the monitoring of molecular alterations after progression to osimertinib.

Betamethasone dipropionate and calcipotriol foam as an adjuvant therapy in patients with severe psoriasis treated with biologic drugs

Betamethasone dipropionate and calcipotriol foam as an adjuvant therapy in patients with severe psoriasis treated with biologic drugs

A Case Study of a Patient Who Discontinued Diuretics due to Hyponatremia and Was Treated with Korean Medicine for Ascites

Objectives: This study examined a case of an 80-year-old woman with extensive ascites and hypervolemic hyponatremia due to decompensated liver cirrhosis.Methods: The patient was first treated with a diuretic to treat her ascites. However, during hospitalization, she developed hypervolemic hyponatremia due to liver cirrhosis. Therefore, we discontinued the diuretic and treated her with Korean herbal medicine (Insamyangyoung-tang with Oryeong-san). We measured her abdominal circumference, followed by radiography, to evaluate the effect of Korean herbal medicine.Result: We treated the patient only with Korean medicine and without diuretics, and her ascites was successfully reduced. No recurrence was observed.Conclusion: Korean herbal medicine can be used as an adjuvant therapy for patients with ascites and hyponatremia.

Interplay between Serotonin, Immune Response, and Intestinal Dysbiosis in Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disorder characterized by periods of activity and remission. IBD includes Crohn's disease (CD) and ulcerative colitis (UC), and even though IBD has not been considered as a heritable disease, there are genetic variants associated with increased risk for the disease. 5-Hydroxytriptamine (5-HT), or serotonin, exerts a wide range of gastrointestinal effects under both normal and pathological conditions. Furthermore, Serotonin Transporter (SERT) coded by Solute Carrier Family 6 Member 4 (SLC6A4) gene (located in the 17q11.1-q12 chromosome), possesses genetic variants, such as Serotonin Transporter Gene Variable Number Tandem Repeat in Intron 2 (STin2-VNTR) and Serotonin-Transporter-linked promoter region (5-HTTLPR), which have an influence over the functionality of SERT in the re-uptake and bioavailability of serotonin. The intestinal microbiota is a crucial actor in normal human gut physiology, exerting effects on serotonin, SERT function, and inflammatory processes. As a consequence of abnormal serotonin signaling and SERT function under these inflammatory processes, the use of selective serotonin re-uptake inhibitors (SSRIs) has been seen to improve disease activity and extraintestinal manifestations, such as depression and anxiety. The aim of this study is to integrate scientific data linking the intestinal microbiota as a regulator of gut serotonin signaling and re-uptake, as well as its role in the pathogenesis of IBD. We performed a narrative review, including a literature search in the PubMed database of both review and original articles (no date restriction), as well as information about the SLC6A4 gene and its genetic variants obtained from the Ensembl website. Scientific evidence from in vitro, in vivo, and clinical trials regarding the use of selective serotonin reuptake inhibitors as an adjuvant therapy in patients with IBD is also discussed. A total of 194 articles were used between reviews, in vivo, in vitro studies, and clinical trials.

Is the (Neo)adjuvant Therapy of Patients with Primary HER2-positive Breast Cancer Cost-Covering?: Process Cost Analysis of Neoadjuvant and Post-Neoadjuvant Systemic Therapy of Patients with Primary HER2-positive Breast Cancer.

Introduction HER2 positivity is one of the most important predictive factors in the treatment of breast cancer patients. Thanks to new targeted anti-HER2 drugs, the prognosis for HER2-positive breast cancer patients has been significantly improved, and the treatment can now be designed according to the risk situation and the response to treatment. At the same time, these innovative targeted anti-HER2 drugs are associated with high costs and require long and involved patient care. Materials and Methods In this paper, we compare the treatment costs of three post-neoadjuvant treatment regimens (trastuzumab vs. trastuzumab/pertuzumab vs. T-DM1) in early stage HER2-positive breast cancer from the perspective of the oncological outpatient clinic of a certified breast center at a university hospital, and evaluate the cost coverage. Results The highest costs in systemic therapy were the material costs. These were the highest for dual blockade with trastuzumab/pertuzumab, followed by T-DM1 and trastuzumab monotherapy. According to our study, all three of these post-neoadjuvant therapy variants achieve a positive contribution margin. While all three models have similar contribution margins, the treatment pathway with T-DM1 is associated with a 30% lower contribution margin. Conclusions Although these model calculations are associated with limitations in view of the introduction of biosimilar antibodies, it can be shown that modern therapeutic approaches do not always have to be associated with lower profits.

296P Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): Updated results from ADAURA

Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI sensitising and EGFR T790M resistance mutations. It has efficacy in EGFRm NSCLC, including in central nervous system (CNS) metastases. In the Phase III ADAURA (NCT02511106) primary analysis adjuvant osimertinib showed a significant and clinically meaningful disease-free survival (DFS) benefit vs placebo (PBO) in pts with completely resected EGFRm (ex19del/L858R) NSCLC, ± adjuvant chemotherapy (CT): stage IIꟷIIIA DFS HR, 0.17; 99.06% CI, 0.11, 0.26; p<0.0001; stage IBꟷIIIA DFS HR, 0.20; 99.12% CI 0.14, 0.30; p<0.0001.

39TiP A phase II study of tislelizumab (TIS) plus sitravatinib as adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risk of recurrence after surgical resection

39TiP A phase II study of tislelizumab (TIS) plus sitravatinib as adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risk of recurrence after surgical resection

C-POST Protocol Update: A Phase 3, Randomized, Double-Blind Study of Adjuvant Cemiplimab vs. Placebo Post Surgery and Radiation Therapy in Patients with High-Risk Cutaneous Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with an incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is >95%, some patients have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Postoperative radiation therapy (RT) is recommended for these patients, but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for patients with high-risk CSCC. Here, we provide a summary of the most recent study protocol amendment. <h3>Materials/Methods</h3> C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for patients with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50 Gy, within 10 weeks before randomization) (NCT03969004). Patients with at least one of the following high-risk features are eligible: (1) nodal disease with (a) extracapsular extension and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of extracapsular extension; (2) in-transit metastases; (3) T4 lesion; (4) perineural invasion; and (5) recurrent CSCC with at least one other risk factor. Patients with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), patients are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), patients in the placebo arm who experience disease recurrence and patients in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. The trial is expected to enroll 412 patients from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival; secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic. <h3>Results</h3> Not applicable (trial in progress) <h3>Conclusion</h3> Not applicable (trial in progress)

Prospective Characterization of Circulating Tumor Cell Kinetics in Patients with Locoregional Head and Neck Cancer Receiving Definitive Therapy

<h3>Purpose/Objective(s)</h3> To characterize circulating tumor cell (CTC) kinetics in response to definitive or adjuvant therapy in patients with locoregional head and neck cancer and identify a profile of CTC kinetics that is associated with favorable disease response. <h3>Materials/Methods</h3> Patients with head and neck cancer of any subsite, excluding cutaneous malignancies, receiving definitive or post-operative adjuvant radiotherapy (RT) with or without concurrent chemotherapy were included. Induction chemotherapy was also permitted. Blood specimens were collected at baseline, during RT, and at routine follow-up visits. CTCs were captured and quantified using a nanotechnology-based assay functionalized with aEpCAM, aHER-2, and aEGFR to facilitate biomimetic cell rolling and dendrimer-mediated multivalent binding. Disease status was assessed per RECIST 1.1 criteria. CTC counts were reported and compared at various follow-up intervals for groups with and without complete response and progression. CTC counts were compared using the Wilcoxon signed rank test. <h3>Results</h3> 33 patients were enrolled with a median follow up of 15 months and median 6 CTC measurements per patient (range, 3-12). Histologies included squamous cell carcinoma (n=30), sinonasal undifferentiated carcinoma (n=1), high grade carcinoma with neuroendocrine features (n=1), and mucoepidermoid carcinoma (n=1). Subsites included the oropharynx (n=23), sinonasal (n=3), larynx (n=2), oral cavity (n=3), nasopharynx (n=1), and unknown primary (n=1). Of 23 oropharyngeal malignancies, 20 were HPV-associated. 25 patients received definitive chemoradiation (CRT), while 8 patients received surgical resection followed by risk-adapted adjuvant RT +/- chemotherapy. For patients treated with definitive CRT, median pre-treatment and end of treatment CTC counts were 77 CTCs/mL (range 7-849) and 22 CTCs/mL (range 2-209), respectively (P = 0.01). For patients treated with post-operative therapy, median pre-treatment and end of treatment CTC counts were 63 CTCs/mL (range 13-182) and 43 CTCs/mL (range 27-150), respectively (P = 0.17). Of 7 patients who developed disease progression and had CTC data available prior to the diagnosis of recurrence, 4 exhibited an increase in CTC counts near the time of progression. In comparison, 85% (17/20) of patients without evidence of disease progression had continued decline or stability of CTC counts following treatment, while the remaining 3 patients exhibited a transient increase in CTC counts. <h3>Conclusion</h3> Our data suggest that CTCs may serve as a biomarker for response to therapy in patients being treated for definitive management of locoregional head and neck cancer. Additional studies are warranted to further characterize their predictive and prognostic value.

Incidence of Cutaneous Adverse Events With Phosphoinositide 3-Kinase Inhibitors as Adjuvant Therapy in Patients With Cancer

ImportanceThe phosphoinositide 3-kinase (PI3K) pathway is among the most frequently activated pathways in human cancers. As the use of PI3K inhibitors for cancer treatment grows, there is increasing need for understanding the cutaneous effects associated with these therapies.ObjectiveTo systematically review the published literature reporting incidence of cutaneous adverse events with PI3K inhibitors and to provide pooled incidence estimates using meta-analysis.Data SourcesThis systematic review and meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The literature search concerned entries through September 2021 in the following sources: PubMed, Cochrane registry, ClinicalTrials.gov, and evidence from the NHS UK and Trip medical database. To analyze PI3K inhibitors’ cutaneous adverse events incidence, only randomized clinical trials (RCTs) were considered. The search strategy used the following keywords: (prevalence OR incidence OR epidemiology) and (phosphoinositide 3 kinase inhibitors OR PI3K inhibitors). No language restriction was applied. Analysis was conducted on July 1, 2022.Study SelectionStudies included phase 2 and phase 3 RCTs that reported incidence of cutaneous adverse events associated with use of PI3K inhibitors.Data Extraction and MeasuresData extracted included sex, medication name and class, sample size, rash incidence, and grade. The bias risk was assessed by the Cochrane tool for risk of bias assessment in RCTs.Main Outcomes and MeasuresThe primary outcome was incidence of PI3K inhibitor cutaneous adverse events (with 95% CIs) among the overall population and among subgroups. Between-study heterogeneity was assessed using the I2 statistic.ResultsThe analysis found the incidence of PI3K inhibitor cutaneous events of any grade to be 29.30% in the intervention group, translating to a pooled odds ratio (OR) for incidence of cutaneous adverse events of any grades of 2.55 (95% CI, 1.74-3.75). Incidence of severe grade (grade ≥3) of rash in the intervention group was estimated to be 6.95%, yielding a pooled Peto OR of 4.64 (95% CI, 2.70-7.97). Subgroup analyses revealed that the incidence of severe cutaneous adverse events (grade ≥3) was higher with the use of Pan-class-1 PI3K inhibitors (OR, 6.67; 95% CI, 4.28-10.38) than isoform-selective PI3K inhibitors (OR, 6.37; 95% CI, 3.25-12.48).Conclusions and RelevanceThis systematic review and meta-analysis identified an overall incidence of PI3K inhibitor cutaneous adverse events of any grade to be 29.30% with a pooled OR of 2.55; (95% CI, 1.74-3.75). These findings clarify the risk of cutaneous adverse events associated with this important class of anticancer therapies.

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P= 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI-0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.

A randomized clinical trial to test efficacy of chamomile and saffron for neuroprotective and anti-inflammatory responses in depressive patients

Depression is one of the common psychiatric problems in growing world population caused by long-term stressful events that may trigger the down regulation of neurogenesis. The pathogenesis of depression initially relies on serotonin deficiency which is associated with depressive feelings. Tryptophan (TRP) depletion participate crucial role in inducing depressive symptoms. Long-term reduction of 5-HT may disseminate to high sensitivity of MDD and alters the level of BDNF. Some studies have also revealed the strong association between excessive neuroinflammation and BDNF levels, due the release of pro-inflammatory cytokines. The treatment approach through FDA approved medicine has their own merits and drawbacks. Therefore, herbal alternatives have recently garnered attention for their effectiveness against depression. However, evidence-based synergic effects of antidepressant with different herbal agents are limited. The purpose of this study was to assess the synergistic effects of two well-known herbs, chamomile and saffron, as an adjuvant therapy in patients with mild to moderate depression. The present study was study randomized, open, blinded trial and comprised of 120 participants randomly allocated to control (n = 60) and test (n = 60). After consent, the patient health questionnaire- 9 (PHQ-9) was filled to obtain depression scores. The test participants were received herbal tea sachets twice a day for one month (20 mg Chamomile and 1 mg Saffron/sachet) along with routine medicines, while control participants were received only allopathic medications. Blood samples were taken before and after the treatment. The depressive symptoms improved significantly with both treatments. The effect of herbs enhanced the efficacy of medications and significantly improved PHQ-9 scale and BDNF while reduced the inflammatory markers (CRP) and TRP level in plasma thereby increased the availability of TRP in brain. It has been concluded that the herbal adjuvant therapy produced long term improvement against depression and enhanced the efficacy of allopathic treatment.

Development and validation of a pre- and intra-operative scoring system that distinguishes between non-advanced and advanced axillary lymph node metastasis in breast cancer with positive sentinel lymph nodes: a retrospective study

BackgroundThere are currently no scoring-type predictive models using only easily available pre- and intraoperative data developed for assessment of the risk of advanced axillary lymph node metastasis (ALNM) in patients with breast cancer with metastatic sentinel lymph nodes (SLNs). We aimed to develop and validate a scoring system using only pre- and intraoperative data to distinguish between non-advanced (≤ 3 lymph nodes) and advanced (> 3 lymph nodes) ALNM in patients with breast cancer with metastatic SLNs.MethodsWe retrospectively identified 804 patients with breast cancer (cT1-3cN0) who had metastatic SLNs and had undergone axillary lymph node dissection (ALND). We evaluated the risk factors for advanced ALNM using logistic regression analysis and developed and validated a scoring system for the prediction of ALNM using training (n = 501) and validation (n = 303) cohorts, respectively. The predictive performance was assessed using the receiver operating characteristic (ROC) curve, area under the curve (AUC), and calibration plots.ResultsUltrasound findings of multiple suspicious lymph nodes, SLN macrometastasis, the ratio of metastatic SLNs to the total number of SLNs removed, and the number of metastatic SLNs were significant risk factors for advanced ALNM. Clinical tumor size and invasive lobular carcinoma were of borderline significance. The scoring system based on these six variables yielded high AUCs (0.90 [training] and 0.89 [validation]). The calibration plots of frequency compared to the predicted probability showed slopes of 1.00 (training) and 0.85 (validation), with goodness-of-fit for the model. When the cutoff score was set at 4, the negative predictive values (NPVs) of excluding patients with advanced ALNM were 96.8% (training) and 96.9% (validation). The AUC for predicting advanced ALNM using our scoring system was significantly higher than that predicted by a single independent predictor, such as the number of positive SLNs or the proportion of positive SLNs. Similarly, our scoring system also showed good discrimination and calibration ability when the analysis was restricted to patients with one or two SLN metastases.ConclusionOur easy-to-use scoring system can exclude advanced ALNM with high NPVs. It may contribute to reducing the risk of undertreatment with adjuvant therapies in patients with metastatic SLNs, even if ALND is omitted.

345. CAMRELIZUMAB AS ADJUVANT THERAPY IN RESECTED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A PHASE 2 TRIAL

Abstract CheckMate 577 has confirmed that adjuvant immunotherapy significantly prolongs disease-free survival (DFS) in patients with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy. However, adjuvant therapy for patients with different neoadjuvant therapies needs to be explored. Therefore, this study was designed to investigate the efficacy and safety of camrelizumab as adjuvant therapy in patients with resected (R0) esophageal squamous cell carcinoma (ESCC). This is an ongoing, non-randomized, open-label, phase 2 trial (NCT04533490) in China. ESCC patients (stage cT1b-T4aN0M0/cT1-T4aN + M0) aged 18–75 years with ECOG performance status of 0–1 was planned to be enrolled in cohort A (n = 42, with 6–12 weeks of neoadjuvant therapy) and cohort B (n = 43, without neoadjuvant therapy). Following R0 resection, adjuvant camrelizumab (200 mg Q2W) was given until tumor recurrence, metastasis, intolerable toxicity, or the completion of 12-month treatment. The primary endpoint was DFS. Secondary endpoints included overall survival, recurrence rate, 1/3/5-year DFS rates, and safety. At data cutoff (Apr 21, 2022), 17 patients were enrolled, with a median age of 65 years; 9 (53%) patients were males, and 12 (71%) had ECOG performance status of 0. There were 15 patients in cohort A (14 with neoadjuvant immunochemotherapy, and 1 with neoadjuvant chemotherapy) and 2 in cohort B. With a median follow-up of 5.5 months, DFS was not reached. A total of 14 (82.3%) patients had treatment-related adverse events, which were all grade 1–2. The most common events were reactive cutaneous capillary endothelial proliferation (11 [65%]), adrenal cortical insufficiency (3 [18%]), and interstitial pneumonia (2 [12%]). Adjuvant camrelizumab showed acceptable safety profile in patients with resected (R0) ESCC who mainly received neoadjuvant immunochemotherapy, and the efficacy was worth expecting. The study enrollment is ongoing, and further survival and safety data will be reported in the future.

Abstract A008: Mechanisms of immune escape in NF1-associated peripheral nerve sheath tumors

Abstract Background: Neurofibromatosis type 1 (NF1) is a neurogenetic condition characterized by neurocognitive symptoms, cutaneous findings, and a predisposition for benign and malignant tumors including peripheral nerve sheath tumors (PNST). About half of patients with NF1 develop plexiform neurofibromas (pNF), non-malignant tumors that often grow rapidly during childhood and can cause significant deformity, disruption of function, and pain. Some lesions, denoted atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), exhibit atypia, loss of neurofibroma architecture, high cellularity and mitotic activity, as an immediate precursor to malignant transformation. For people with NF1 there is a 10-15% overall lifetime risk of developing the aggressive soft tissue sarcoma malignant peripheral nerve sheath tumors (MPNST). Despite many clinical trials of chemotherapy and targeted agents, there has been little advancement in treatment outcomes and overall patient survival remains poor; therefore, new therapeutic approaches are needed. PNST are made up of transformed Schwann cell precursors, which do not grow and survive in isolation but rather interact with infiltrating immune cells. A deeper understanding of the relationship between the pre-existing immunity and the tumor microenvironment (TME) will help unveil potential for new combinations and adjuvant therapies for patients with PNST. Methods: We have developed a unique Johns Hopkins biospecimen repository of human NF1-associated PNST specimens. We use quantitative and spatial resolution of the geography and nature of tumor infiltrating immune cells in human PNST and have determined the interactions of T cells, myeloid cells, and immunoregulatory molecules, using a combination of multiplex chromogenic, high-dimensional flow cytometry and gene expression profiling studies. We have also analyzed existing transcriptomic datasets from 21 pNF and 34 MPNST cases. Results: RNA sequence analysis revealed an accumulation of immunosuppressive Th2 cells and tumor infiltrating myeloid cells (TIM) in the TME of PNST, which we postulate generates an anti-inflammatory response against tumors. Immunophenotyping of 17 pNF, 8 ANNUBP, and 15 MPNST human specimens confirmed the higher presence of infiltrating myeloid compared to lymphoid cells, with a predominance of CD163+ myeloid cells (TIM) during progression to malignancy. We also detected a significant increase in regulatory T cells and cytotoxic CD8+ T cells in MPNST vs ANNUBP vs pNF and near absence of CD19+ B cells in all tumor types. Multiparameter flow cytometry of single cells suspensions are being studied to further investigate the association of myeloid inflammation leading to the immune evasion of PNST. Conclusions: An immunosuppressive microenvironment characterizes PNST during the process of malignant transformation, generating an immune-excluded phenotype. Leveraging the immune contexture and the mechanisms of immune modulation in PNST will inform interventions to stimulate anti-tumor immunity in this dire disease. Citation Format: Lindy Zhang, Kai Pollard, Ana Calizo, Alexandre Maalouf, Aditya Suru, Jiawan Wang, Jineeta Banerjee, Christine A. Pratilas, Nicolas J. Llosa. Mechanisms of immune escape in NF1-associated peripheral nerve sheath tumors [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr A008.

948TiP Efficacy and safety of almonertinib in the adjuvant treatment of resectable stage I non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-sensitizing mutations in solid and/or micropapillary components

Pathological subtypes are prognostic indicators independent of TNM stage, and patients with micropapillary and solid components have poorer prognosis. Previous studies have found that the presence of a micropapillary component was significantly associated with worse recurrence-free survival in patients with stage I lung adenocarcinoma, even the components are less than 5%, and postoperative adjuvant chemotherapy can still bring benefit to those patients even with stage IA. Third-generation EGFR-TKI have recently shown striking benefit for postoperative adjuvant therapy in patients with EGFR-mutated NSCLC. At present, there is no systematic study on the efficacy and safety of third-generation EGFR-TKI in stage I NSCLC patients with high-risk recurrence factors, such as solid and micropapillarycomponents. The third-generation EGFR-TKI, aumolertinib(HS-10296), showed promising efficacy in advanced NSCLC patients with sensitive EGFR mutation. This is the first study to explore the efficacy and safety of aumolertinib as adjuvant therapy in patients with EGFR mutant stage I NSCLC with solid and/or micropapillary component. Approximately 52 stage I EGFR-mutated NSCLC patients with solid and/or micropapillary components ≥10% will be enrolled in this multicenter single-arm study. After radical lung cancer surgery, they will receive oral almonertinib 110 mg/d as adjuvant therapy for 3 years. The primary endpoint is 2-year disease free survival (DFS) rates, and secondary endpoints included the 3-, 4-, and 5-year DFS rates, 5-year overall survival rates, safety and quality of life, Circulating tumor DNA will also be monitored during the study. Recruitment of this study is ongoing, and the first patient had been enrolled in January 2022. The author.

1297P Adjuvant gemcitabine is as efficient as mFOLFIRINOX in patients with GemPred+ tumor signature and resected pancreatic adenocarcinoma (PDAC): An ancillary study of the PRODIGE-24 clinical trial

GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids, and validated retrospectively (Nicolle et al). The phase 3 PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified FOLFIRINOX (mFFX) over GEM as adjuvant therapy in patients with resected PDAC at the expense of higher toxicity (Conroy et al). We evaluated the potential theranostic value of GemPred in this population.

LBA66 IMmotion010: Efficacy and safety from the phase III study of atezolizumab (atezo) vs placebo (pbo) as adjuvant therapy in patients with renal cell carcinoma (RCC) at increased risk of recurrence after resection

The standard of care for loco-regional RCC is nephrectomy, but many patients (pts) experience recurrence. IMmotion010, a Phase III, multicentre, randomised, pbo-controlled, double-blinded trial, evaluated atezo (anti-PD-L1) monotherapy as adjuvant therapy in pts with RCC and increased risk of recurrence after resection.

LBA49 CANOPY-A: Phase III study of canakinumab (CAN) as adjuvant therapy in patients (pts) with completely resected non-small cell lung cancer (NSCLC)

CAN is a high-affinity anti-IL–1β antibody that was superior to placebo (PBO) at preventing cardiac adverse events (AEs) in the CANTOS study. In an exploratory analysis of CANTOS, CAN was associated with significant reductions in NSCLC incidence and mortality, suggesting that CAN inhibition of the IL-1β pathway may have reduced the rate of progression, invasiveness, and metastatic spread of lung cancers undiagnosed at trial entry. Here, we show efficacy and safety of CAN as adjuvant therapy vs PBO in pts with completely resected NSCLC.

LBA47 Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): Updated results from ADAURA

Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI sensitising and EGFR T790M resistance mutations. It has efficacy in EGFRm NSCLC, including in central nervous system (CNS) metastases. In the Phase III ADAURA (NCT02511106) primary analysis adjuvant osimertinib showed a significant and clinically meaningful disease-free survival (DFS) benefit vs placebo (PBO) in pts with completely resected EGFRm (ex19del/L858R) NSCLC, ± adjuvant chemotherapy (CT): stage IIꟷIIIA DFS HR, 0.17; 99.06% CI, 0.11, 0.26; p<0.0001; stage IBꟷIIIA DFS HR, 0.20; 99.12% CI 0.14, 0.30; p<0.0001. We report updated exploratory analyses of DFS and recurrence patterns after 2 yrs added follow up. Eligible pts (aged ≥18 yrs [≥20 in Japan/Taiwan], WHO PS 0/1, completely resected EGFRm stage IBꟷIIIA [AJCC 7th edition] NSCLC; adjuvant CT allowed) were randomised 1:1 to osimertinib 80 mg once daily or PBO for up to 3 yrs. Primary endpoint: investigator-assessed DFS in stage IIꟷIIIA. Secondary endpoints: DFS in stage IBꟷIIIA, overall survival and safety. Patterns of recurrence and CNS DFS were pre-specified exploratory endpoints. Data cut-off: 11 April 2022. Globally, 682 pts were randomised; osimertinib n=339, PBO n=343. In this updated analysis, in pts with stage IIꟷIIIA disease DFS HR was 0.23 (95% CI 0.18, 0.30; 242/470 events; 51% maturity); 3-yr DFS rate was 84% with osimertinib vs 34% with PBO. In the overall population (stage IBꟷIIIA) DFS HR was 0.27 (95% CI 0.21, 0.34; 305/682 events); 3-yr DFS rate was 85% with osimertinib vs 44% with PBO. In the osimertinib arm, fewer pts experienced local/regional and distant recurrence vs PBO. CNS DFS HR was 0.24 (95% CI 0.14, 0.42; 63/470 events) in stage IIꟷIIIA. The long-term safety profile remains consistent with the known profile of osimertinib. With 2 yrs further follow-up, a continued DFS benefit was sustained with osimertinib vs PBO, consistent with the primary analysis. These mature data reinforce adjuvant osimertinib as standard of care for pts with EGFRm stage IB–‍IIIA NSCLC after complete tumour resection and adjuvant CT, when indicated.