Immunotherapy Trials Research Articles

IMMULAB: A phase II trial of immunotherapy with pembrolizumab in combination with local ablation for patients with early stage hepatocellular carcinoma (HCC)—The IKF-IMMULAB trial.

582 Background: Ablation of neoplastic tissue through radiofrequency ablation (RFA), microwave ablation (MWA), or brachytherapy is a potentially curative option for patients with early stage hepatocellular carcinoma (HCC); however, recurrence rates are high. While updated results from IMbrave050 do not support the use of adjuvant therapy following resection or local therapy, the potential of peri-interventional systemic treatment as a potentially more effective approach to increase recurrence free and long-term survival remains to be determined. We propose that peri-interventional treatment with pembrolizumab may improve outcomes following local ablative therapies. Methods: This single arm phase II trial investigates peri-interventional treatment with pembrolizumab combined with RFA/MWA or brachytherapy, or - as recommended for tumors ≥ 3 cm - by combination with TACE in early stage HCC with maintained liver function. 200 mg of pembrolizumab (q3w) was administered intravenously for 2 cycles followed by radiologic imaging and local therapy. Pembrolizumab was continued for up to 12 months. Primary endpoint was radiological response rate according to RECIST 1.1 prior to local therapy. Results: 30 pts (ECOG 0 or 1) were enrolled in 9 centers in Germany with a median age of 70 years (73.3% males, median tumor size 25 mm with minimum of 10 mm and maximum of 72 mm, 60% solitary lesions). All pts received at least 1 dose of study treatment and the median number of cycles was 13. ORR was 13.3% with 6.7% CR and 6.7% PR after two cycles. After a median follow-up of 34.5 months, median time to recurrence (TTR) was 16.43 months, with 8 pts remaining free of recurrence. mOS was not reached, with a 2y OS rate of 76% and a 3y OS rate of 66%. No new safety signs were observed. Subsequent local ablation was performed in 13 pts, and 10 pts started on systemic therapies (5 TKI, 3 ICI and 2 pts received TKI and ICI). Conclusions: In the IKF-IMMULAB trial the expected objective response rate of 30%, according to RECIST1.1., prior to local therapy was not reached. However, with recent evidence that radiologic response underestimates pathological response in ICI-treated HCC patients and supported by a 2y OS rate of 76% and a 3y OS rate of 66%, there is evidence for the efficacy of peri-interventional treatment with pembrolizumab without new safety signals. Clinical trial information: NCT03753659 .

What Is the Role of Fecal Microbiota Transplantation in Immunotherapy Trials? Current Perspectives and Future Directions.

Immune checkpoint inhibitors (ICIs) are rapidly transforming the treatment landscape of genitourinary and other immunogenic malignancies. Despite these advances, biomarkers for the prediction of ICI response remain to be established. The gut microbiome has been identified as a modulator of immune regulation and a potential regulator of response to ICIs. Fecal microbiota transplantation (FMT) has emerged as a potential novel therapeutic tool to enhance ICI response, as demonstrated in several trials, spanning across genitourinary malignancies as well as others. While safety and clinical potential of FMT have been demonstrated, FMT parameters including optimal treatment regimens, bowel preparation protocols, patient selection, and donor-host compatibility need to be defined. Furthermore, targeted interventions including probiotic supplementation represent promising therapeutic avenues meriting further study.

Emerging Immunotherapies for Disease Modification of Type 1 Diabetes.

Type 1 diabetes mellitus (T1DM) is characterized by the progressive, autoimmune-mediated destruction of β cells. As such, restoring immunoregulation early in the disease course is sought to retain endogenous insulin production. Nevertheless, in the more than 100 years since the discovery of insulin, treatment of T1DM has focused primarily on hormone replacement and glucose monitoring. That said, immunotherapies are widely used to interdict autoimmune and autoinflammatory diseases and are emerging as potential therapeutics seeking the preservation of β-cell function among those with T1DM. In the past 4 decades of diabetes research, several immunomodulatory therapies have been explored, culminating with the US Food and Drug Administration approval of teplizumab to delay stage 3 (clinical) onset of T1DM. Clinical trials seeking to prevent or reverse T1DM by repurposing immunotherapies approved for other autoimmune conditions and by exploring new therapeutics are ongoing. Collectively, these efforts have the potential to transform the future of diabetes care. We encapsulate the past 40 years of immunotherapy trials, take stock of our successes and failures, and chart paths forward in this new age of clinically available immune therapies for T1DM.

Abstract B003: Landscape of chemoradiation plus immunotherapy trials across multiple locally advanced cancer types: The more, the better?

Abstract Purpose: Checkpoint inhibitors (ICIs) are being added to standard-of-care chemoradiotherapy in multiple clinical trials. The optimal sequencing of immunotherapy and chemoradiotherapy remains widely debated. Therefore, we compiled available trials and reviewed various aspects that may be associated with outcomes. Methods: We conducted a systematic literature review of randomized controlled Phase 3 trials (RCTs) in PubMed, ClinicalTrials.gov and Google scholar from 1/1/2018 to 11/8/2024. We included all available seminal randomized controlled trials with matured data, encompassing locally advanced non–small and small cell lung carcinomas, head and neck, endometrial and cervical cancers treated with chemoradiotherapy plus ICI. Performance of these trials with different ICI timing was analyzed in a high level and stratified by radiation treatment sites, oncovirus driven histology, anti PD1/PD-L1 agents and treatment discontinuation rate. Results: Eleven seminal randomized clinical trials across 6 different cancer types with 7891 patients were included. Among 5 trials with thoracic RT, 2 trials(PACIFIC and ADRIATIC) with only consolidative design proved PFS superiority over placebo, while PACIFIC-2 and LU-005 with concurrent and maintenance design did not. Moreover, CheckMate-73L failed to prove the superiority of concurrent and maintenance ICI over consolidative ICI. Among 3 head & neck trials all with induction + concurrent + maintenance design, only CONTINUUM trial treating nasopharyngeal cancer with 3 cycles of induction ICI proved EFS superiority. Among 3 gynecological trials all with concurrent + maintenance design, only anti PD-1 agent showed PFS superiority in cervical cancer (KEYNOTE-A18) and dMMR endometrial cancer (KEYNOTE-B21) in pre-planned analysis. The trials with concurrent ICI approaches failed in all non-viral driven cancers (NSCLC, SCLC and overall endometrial), but succeeded in EBV-rich Asian nasopharyngeal cancer (CONTINUUM) and HPV-driven cervical cancer (KEYNOTE-A18 and CALLA post hoc analysis of PD-L1 TAP ≥20%). However, this success was not found in HPV-driven head & neck squamous cell cancer (HPV subgroup of either KEYNOTE-412 or JAVELIN). For consolidative ICI trials in thorax, the treatment discontinuation rate was significantly lower in experimental arm compared to control arm (population weighted p=0.0003), mainly due to less tumor progression. For the trials with concurrent ICI, the treatment discontinuation rate was significantly higher in experimental arm (population weighted p=0.001), mainly due to more adverse events. Conclusion: Despite multifactorial heterogeneity, this review provides insights for designing future trials in locally advanced cancers. Consolidative ICI approaches generally showed superiority in thoracic cancers, while concurrent ICI approaches often failed in non-viral-driven cancers likely due to higher adverse events and discontinuation rates but showed efficacy in EBV-rich nasopharyngeal and HPV-driven cervical cancers. As more trial data matures, the existing trends will be further tested. Citation Format: Bin Gui, Bhupesh Parashar. Landscape of chemoradiation plus immunotherapy trials across multiple locally advanced cancer types: The more, the better? [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B003.

Disparities in utilization of novel cancer therapies in advanced stage III and IV melanoma and variance in outcomes.

Significant gains in advanced melanoma have been made through immunotherapy trials. Factors influencing equitable access and survival impact of these novel therapies are not well-defined. Retrospective analysis using National Cancer Database of patients with advanced stage III and IV melanoma from 2004 to 2021. Multivariable logistic regression was used to study the use of immunotherapy and Cox proportional hazard regression to evaluate overall survival (OS). 47,427 patients with increasing utilization of immunotherapy from 13.78% in 2004 to 65.88% by 2021. Inequitable adoption were impacted by age, sex, socioeconomic status/affordability, insurance types and residential educational/income level. Receiving immunotherapy was associated with a 44% improvement in OS (HR 0.56, 95% CI 0.54-0.57) and receiving a clinical trial-based therapy was associated with a 37% improvement (HR 0.63, 95% CI 0.53-0.75). Among patients who received immunotherapy or clinical trial-base therapy, there was 40% worse survival in non-Hispanic Black patients (HR 1.40, 95% CI 1.16-1.69) compared to non-Hispanic Whites. There are disparities in utilization of immunotherapy that is influenced by socioeconomic status. Race and ethnicity had a significant influence in differential impact on survival outcomes of immunotherapies highlighting the importance of increasing underrepresented population participation in trials that lead to novel therapies.

Characteristic of Immunotherapy Trials in Head and Neck Squamous Cell Carcinoma: 2013-2023.

This research provides a comprehensive analysis of immunotherapy clinical trials for head and neck squamous cell carcinoma, aiming to enhance future trial designs. We analyzed all clinical trials focused on head and neck squamous cell carcinoma immunotherapy registered on ClinicalTrials.gov from January 1st, 2013, to December 31st, 2023, examining general characteristics, methodological features, and types of immunotherapeutic drugs. The analysis included 727 trials, with 687 interventional (94.50%) and 40 observational (5.50%). Most trials were small-sized (64.37%), single-centered (56.67%), non-blinded (94.76%), and non-randomized (72.93%). Over half of the trials were conducted in North America (55.71%), but trials in Asia increased significantly in the past 5 years (9.88% vs. 32.38%, p < 0.001). Only 20.63% of completed trials updated outcomes, with most results published 6-12 months after primary completion (55.13%). Immune checkpoint inhibitors were the predominant focus, and neoadjuvant immunotherapy was the main regimen in trials with resectable head and neck squamous cell carcinoma (74.83%). There has been a gradual increase in clinical trials over the past decade, with most being interventional. Delays or absences in outcome submission were prevalent. Novel immunotherapeutic drugs and treatment regimens are a significant focus.

Current and future immunotherapy for breast cancer.

Substantial therapeutic advancement has been made in the field of immunotherapy in breast cancer. The immune checkpoint inhibitor pembrolizumab in combination with chemotherapy received FDA approval for both PD-L1 positive metastatic and early-stage triple-negative breast cancer, while ongoing clinical trials seek to expand the current treatment landscape for immune checkpoint inhibitors in hormone receptor positive and HER2 positive breast cancer. Antibody drug conjugates are FDA approved for triple negative and HER2+ disease, and are being studied in combination with immune checkpoint inhibitors. Vaccines and bispecific antibodies are areas of active research. Studies of cellular therapies such as tumor infiltrating lymphocytes, chimeric antigen receptor-T cells and T cell receptor engineered cells are promising and ongoing. This review provides an update of recent major clinical trials of immunotherapy in breast cancer and discusses future directions in the treatment of breast cancer.

Immune-molecular interactions in high-grade serous ovarian cancer distinguish long-term survivors.

The approach and efficacy of treatments for high-grade serous carcinoma (HGSC) of the ovary have changed little in decades. Although numerous studies demonstrated immune infiltration as frequent and prognostically beneficial, clinical trials of immunotherapies have generated benefit in fewer than 15% of patients. In this issue of the JCI, Nelson and colleagues compiled 1,233 HGSC samples from patients across four continents and compared the molecular and immunologic features that associate with long-term survival (greater than 10 years). Diversity among HGSC tumors is well defined, but this study explored the combined influence of immunologic and molecular features. Long-term survivors harbored tumors with high epithelial content and overrepresentation of the C4/differentiated molecular signature, with cytotoxic T and B cells infiltrating to the tumor epithelium and stroma, respectively. These findings highlight features that might underly poor responsiveness to existing immunotherapies of most HGSC tumors and considerations for the design of future, more precise treatments for HGSC.

A Phase II Open-Label, Randomized Clinical Trial of Atezolizumab with or without Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer.

Advanced urothelial cancer generally has high mortality despite modern anti-PD-1/L1 antibody-based combinations. Augmenting checkpoint inhibitor-mediated immune responses with lymphocyte growth factors may improve outcomes. We conducted a randomized phase II study (Cancer Immunotherapy Trials Network-14) in 47 patients to explore whether human recombinant IL-7 (CYT107) could be safely combined with PD-L1 inhibition to enhance responses. Patients with urothelial cancer after platinum chemotherapy were randomized to atezolizumab alone or with CYT107 weekly for four doses. The primary objective was clinical efficacy by the objective response rate (ORR). Secondary objectives included safety, toxicity, and other clinical outcomes. Correlative endpoints included peripheral immunophenotyping and quantification of cytokines. CYT107 plus atezolizumab was well-tolerated, without dose-limiting toxicities and lower grade 3 to 4 treatment-related adverse events compared with atezolizumab monotherapy. The ORR was 26.3% for the combination therapy versus 23.8% for atezolizumab alone (P = 0.428). The complete response rate was 10.5% for the combination therapy versus 4.8% for monotherapy. Three patients on combination therapy had responses >21 months versus one with monotherapy. CD4+ and CD8+ T-lymphocyte expansion occurred in patients with response to combination therapy, with the greatest effect in T memory stem cells. Patients who responded to treatment exhibited elevated baseline levels of CCL4 and reduced levels of VEGFA and TNF. Combining CYT107 with atezolizumab was safe and resulted in lymphocyte expansion, a doubling of the complete response rate, and durable responses exceeding 2 years. However, the ORR was similar to atezolizumab alone. Increased and sustained doses of CYT107 coupled with patient selection strategies should be further investigated.

Integrative multi-omics analysis uncovers tumor-immune-gut axis influencing immunotherapy outcomes in ovarian cancer

Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We performed comprehensive molecular, immune, microbiome, and metabolic profiling on samples of trial patients. Here, we show increased T and B cell clusters and distinct microbial patterns with amino acid and lipid metabolism are linked to exceptional clinical responses. This study suggests the immune milieu and host-microbiome can be leveraged to improve antitumor response in future immunotherapy trials.

Association of Lung Immune Prognostic Index (LIPI) with Disease Control Rate and Progression-Free Survival in Patients with Soft-Tissue Sarcoma Treated with Immunotherapy in Early-Phase Trials.

The efficacy of immunotherapies in soft-tissue sarcomas (STSs) is limited, and biomarkers of response are lacking. The lung immune prognostic index (LIPI) is a prognostic biomarker used with immunotherapy across cancer types. This study investigates the association of LIPI with the disease control rate (DCR) and progression-free survival (PFS) in patients with STS treated with immunotherapy versus other therapies in early-phase trials. This post hoc analysis was conducted with patients with STS from Gustave Roussy and Centre Léon Bérard between January 2012 and June 2021. The LIPI was calculated based on a derived neutrophil-to-lymphocyte ratio > 3 and elevated lactate dehydrogenase. Patients were categorized based on treatment (immunotherapy or other) and LIPI (good, intermediate, or poor). DCR was defined as the sum of stable disease and complete and partial response. A total of 82 patients were enrolled in immunotherapy trials and 126 in the other therapy trials. In the immunotherapy group, DCR was higher in patients with good LIPI (76%; n = 23/30) compared with the intermediate (50%; n = 13/26) and poor LIPI groups (8%; n = 1/12; p < 0.001). The other-therapy group did not show significant differences in DCR by LIPI: DCR was 70% (n = 48/69), 70% (n = 21/30), and 60% (n = 6/10) in patients with good, intermediate, and poor LIPI, respectively (p = 0.86). In multivariate analyses, LIPI was independently associated with PFS in the immunotherapy group (hazard ratio = 5.97, p = 0.0001) and not in the control group (p = 0.71). LIPI is a significant independent prognostic marker for DCR in patients with STS treated with immunotherapy. In early-phase trials, LIPI could be used as a screening tool for stratification at inclusion. High neutrophil levels, which correlate with a poorer LIPI score, are likely associated with immunotherapy resistance. This relationship could explain the statistical impact of poor LIPI in the immunotherapy group.

"Paradoxical” Cerebral Volume Changes in Anti‐Amyloid Immunotherapy Trials

"Paradoxical” Cerebral Volume Changes in Anti‐Amyloid Immunotherapy Trials

Cancer research in South Asian Association for Regional Cooperation (SAARC) countries.

Cancer is a major global health threat, with 35 million new cases projected by 2050, predominantly in low-income and middle-income-countries. Within South Asian Association for Regional Cooperation (SAARC) countries, a notable gap in cancer research investment and output compared with high-income countries highlights the need to strengthen research capacity. The rising cancer incidence across SAARC countries is not being matched by local research, particularly in clinical trials in molecular biology, targeted therapy, immunotherapy, and cancer vaccines. This paucity of research is problematic as guidelines and therapies developed in high-income countries might not be directly applicable to low-income and middle-income countries due to distinct regional sociocultural, genetic, and environmental factors and are often impractical in these countries due to cost and implementation challenges. This Series paper examines the cancer research landscape within SAARC countries, focusing on Bangladesh, Nepal, Sri Lanka, India, Pakistan, Afghanistan, Bhutan, and Maldives. We analyse PubMed publication rates and examine available infrastructure, current research (including clinical trials), and limitations and disparities among SAARC countries in terms of cancer research. Key challenges include disparities in health-care access, cultural and economic barriers, and little funding and infrastructure. Strengthening cancer research in SAARC countries requires building collaborative networks, improving research facilities and training, focusing on local epidemiological studies, and developing affordable technologies and treatments. Effective policy and stakeholder engagement could greatly advance cancer care in the region.

Immunotherapy for Head and Neck Squamous Cell Carcinoma: Present and Future Approaches and Challenges.

Despite significant progress and improving outcomes in the management of head and neck squamous cell carcinoma (HNSCC), there are few effective treatment options for patients with recurrent or metastatic head and neck squamous cell carcinoma. The advent of immune checkpoint inhibitors has changed the treatment algorithm of head and neck squamous cell carcinoma and are approved in the frontline setting for recurrent and metastatic (R/M) head and neck squamous cell carcinomas. Although promising for some patients, most patients with R/M HNSCC do not derive clinical benefit from currently approved checkpoint inhibitors. Many studies are underway to identify the patient population that would benefit the most from immunotherapy as well as postimmunotherapy treatment failures, including novel combinations of immunomodulatory therapies. In this review, we summarize the clinical development of all major clinical trials of immunotherapy in HNSCC.

Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer’s disease, positive for plasma p-tau217

BackgroundThe spread of tau pathology closely correlates with the disease course and cognitive decline in Alzheimer’s disease (AD). Tau-targeting immunotherapies are being developed to stop the spread of tau pathology and thus halt disease progression. In this post hoc analysis of the ADAMANT clinical trial, we examined the performance of AADvac1, an active immunotherapy targeting the microtubule-binding region (MTBR) of tau, in a subgroup of participants with elevated plasma p-tau217, indicating AD-related neuropathological changes.MethodsADAMANT was a 24-month, randomized, placebo-controlled, parallel-group, double-blinded, multicenter, phase 2 clinical trial in subjects with mild AD. The trial participants were randomized 3:2 to receive six doses of AADvac1 or placebo at 4-week intervals, followed by five booster doses at 14-week intervals. The primary outcome was safety. The secondary outcomes were the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer’s Disease Cooperative Study – Activities of Daily Living score for Mild Cognitive Impairment 18-item version (ADCS-ADL-MCI-18), and immunogenicity. Volumetric MRI, plasma neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were exploratory outcomes. The inclusion criterion for this post-hoc analysis was a baseline plasma p-tau217 level above the cutoff for AD.ResultsAmong 196 ADAMANT participants, 137 were positive for plasma p-tau217 (mean age 71.4 years, 59% women). AADvac1 was safe and well tolerated in this subgroup. AADvac1 reduced the rate of accumulation of log-plasma NfL by 56% and that of GFAP by 73%. The treatment differences in the CDR-SB and ADCS-ADL-MCI-18 scores favored AADvac1 but were not statistically significant. AADvac1 had no effect on whole-brain volume but nonsignificantly reduced the loss of brain cortical tissue in several regions. Importantly, the impact on the study outcomes was more pronounced in participants with higher anti-tau antibody levels.ConclusionsThese results suggest that AADvac1 tau immunotherapy can reduce plasma biomarkers of neurodegeneration and neuroinflammation. These findings and possible observations on brain atrophy and cognition are hypothesis-generating and warrant further evaluation in a larger clinical trial.Trial registrationEudraCT 2015–000630-30 (primary) and NCT02579252.

THOR: a TMB heterogeneity-adaptive optimization model predicts immunotherapy response using clonal genomic features in group-structured data.

With the increasing number of indications for immune checkpoint inhibitors in early and advanced cancers, the prospect of a tumor-agnostic biomarker to prioritize patients is compelling. Tumor mutation burden (TMB) is a widely endorsed biomarker that quantifies nonsynonymous mutations within tumor DNA, essential for neoantigen production, which, in turn, correlates with the immune response and guides decision-making. However, the general clinical application of TMB-relying on simple mutational counts targeted at a single endpoint-does not adequately capture the complex clonal structure of tumors nor the multifaceted nature of prognostic indicators. This recognition has spurred the exploration of sophisticated high-dimensional regression techniques. Unfortunately, the limited cohort sizes in immunotherapy trials have hindered the full potential of these advanced methods. Our approach considers patient subgroups as related yet distinct entities, enabling precise tailoring and refinement to address subgroup-specific dynamics. Given the deficiencies and the constraints, we introduce a TMB heterogeneity-optimized regression (THOR). This innovative model enhances the predictive capabilities of TMB by integrating tumor clonality and a diverse spectrum of clinical endpoints, further augmented by fusion techniques across subgroups to facilitate robust data sharing and interpretation. Our simulations validate THOR's superiority in parameter estimation for statistical inference. Clinically, we assess the utility of THOR in a structured cohort of 238 cancer patients undergoing immunotherapy, supplemented by 2212 patients across 19 subgroups from public datasets. The forecast of the responses and comparison of survival hazards demonstrate that THOR significantly enhances patient stratification and prognostic predictions by incorporating complex immunogenetic biology and subgroup-specific dynamics.

Patient and Caregiver Experience of Diagnosis, Treatment, and Living With Recurrent Oropharyngeal Cancer

The management of recurrent oropharyngeal cancer (rOPC) is complex. Curative options carry considerable risk of morbidity with overall poor prognosis. Little data exist on function and quality of life (QoL) outcomes for noncurative treatments. Even less is known about patient and carer experiences of function and QoL change over time when undergoing curative or noncurative treatment(s) for rOPC. To investigate the patient and caregiver experience of diagnosis, treatment, and living with recurrent oropharyngeal cancer and changes to function/QoL. A longitudinal prospective and retrospective qualitative study was carried out at a specialist cancer center in the United Kingdom. Participants with a biopsy proven diagnosis of recurrent OPC and their caregivers were included. Participants were recruited between December 2022 and November 2023. Concurrent data analysis took took place between November 2023 and January 2024. Curative salvage surgery or noncurative immunotherapy, chemotherapy, or clinical trials of investigational agents. A framework-approach thematic analysis of semistructured, in-depth interviews. Twenty-two patients and 7 caregivers were recruited. Demographic data was collected via medical record review. The longitudinal sample included 8 male and 2 female individuals, and the median age was 62 (range, 47-77) years. The retrospective sample included 11 male individuals and 1 female individual, and the median age was 64 (range, 59-70) years. Eleven participants (50%) underwent curative treatment, and 11 (50%) noncurative treatment.Treatments included salvage surgery, immunotherapy, chemotherapy, or clinical trials. Patients and their caregivers contextualize their experience of recurrent disease in their past experience of primary disease diagnosis and treatment. Patients want to survive and when the options to choose between are cure or functional outcomes impacting health-related QoL, cure appears to be favored. However, when cure is not an option, patients appear to want to survive as long as possible. However, as the prognosis gets shorter there appears to be a shift in priorities where function/QoL take precedence over survival. This qualitative study found that treatment decision-making is extremely complex in the setting of rOPC. Quite often, decisions are made based on what is perceived by health care professionals to be functionally "too morbid" with salvage surgery, or "kinder" with life-prolonging noncurative treatments. However, patients are not always fully involved in these decisions and so shared decision-making does not always happen. To facilitate shared decision-making and informed consent, patients need to be given clear and accurate information on survival and function/QoL outcomes for the various treatment modalities for rOPC.

Immunotherapy in Oral Cancer

Abstract Squamous cell carcinoma of the head-and-neck (HNSCC) ranks sixth in global cancer incidence and poses significant challenges in terms of morbidity and mortality. The tumor microenvironment in HNSCC is a complex milieu involving immune cells, stromal elements, and cytokines, among other factors. Immunotherapy has emerged as a potent therapeutic avenue, particularly through immune checkpoint inhibitors (ICIs), for modulating this intricate environment. ICIs have garnered approval for first-line use in recurrent and metastatic HNSCC. However, recent clinical observations underscore the variability in treatment response to immunotherapy. This necessitates a thorough exploration of diverse ICI agents and combination strategies to optimize therapeutic outcomes. A comprehensive assessment and focused investigation of the immune contexture in HNSCC patients undergoing ICI therapy are pivotal for advancing treatment efficacy. Numerous innovative immunotherapeutic modalities, including chimeric antigen receptor-T-cell therapy, oncolytic virus therapy, and vaccination strategies, are actively under development. Furthermore, identifying robust biomarkers to guide patient selection for immunotherapy is of paramount importance. The quest for optimal combination regimens incorporating novel immunotherapies represents a recent paradigm shift in the management of HNSCC. This review is a concise summary of the clinical progress and ongoing trials in immunotherapy for HNSCC, highlighting the dynamic landscape of treatment approaches in this challenging disease context.

Brief Report: Should a prior cancer history be reevaluated as an exclusion for clinical trial participation?

BackgroundClinical trials are designed to minimize factors capable of influencing patient outcomes beyond the specific diseases and treatments being studied; however, exclusion of prior cancer (PC) patients could potentially affect the generalizability of study results. We attempted to create a real-world proxy of recent immunotherapy trials in stage III and IV Non-Small Cell Lung Cancer (NSCLC) to understand the relevance of a PC history using the National Cancer Database. MethodsPatients diagnosed between 2017 and 2020 were stratified by the presence of a prior cancer history and propensity matched to compare receipt of immunotherapy with those who did not. We analyzed overall survival using Kaplan Meier analysis and Cox proportional hazards models. ResultsThe addition of immunotherapy to a regimen of chemotherapy and radiation was associated with superior survival whether stage III NSCLC patients had a PC history (HR): 0.65 (95% CI 0.59, 0.71) or had no PC history (HR:0.69 95% CI: 0.66, 0.72). The addition of immunotherapy was also associated with superior survival for stage IV patients with a PC history (HR) 0.78 95% CI 0.72, 0.85) or without PC history (HR:0.75 95% CI: 0.73, 0.78). DiscussionExamination of real-world outcomes of two practice-changing trial regimens found the innovative treatment approach to be superior, regardless of patient PC history. Risk for a second malignancy is a reality of improving cancer treatment, thus, to individualize treatment for patients based on their personal and tumor attributes, cancer survivors will need to be included in trials.

DISP-16. EXPLORING SEX-BASED DIFFERENCES IN RESPONSE TO IMMUNOTHERAPY IN GLIOBLASTOMA: A RETROSPECTIVE REVIEW

Abstract BACKGROUND The prognostic implication of sex is unclear in glioblastoma. A recent preclinical study suggested that T-cell exhaustion in males confers improved response to anti-PD1 therapy (PMID: 37378557). We conducted a retrospective study of patients with newly diagnosed (nGBM) and recurrent (rGBM) glioblastoma enrolled on immunotherapy trials at Dana-Farber Cancer Institute from 2014 to 2022 to determine whether sex influences the response to immunotherapy. METHODS Clinical, molecular, and radiographic data were collected, and their association with progression-free survival (PFS) and overall survival (OS) was evaluated using log-rank. RESULTS We evaluated 299 subjects with nGBM (172 male, 127 female) and 539 with rGBM (329 male, 210 female). In the nGBM cohort, median PFS for males vs females was 9.1 [7.2, 13.8] months vs 8.8 [6.5, 10.1] months (p=0.59) among subjects on immunotherapy trials (N=106), and 6.9 [6.1, 8.0] vs 6.5 [5.8, 8.1] months (p=0.44) in those on non-immunotherapy trials (N=193). Median OS was 18.6 [15.4, 24.0] in males vs 18.8 [15.9, 23.1] months in females (p=0.85) in immunotherapy trials and 15.6 [14.7, 17.3] vs 15.3 [13.1, 16.9] months (p=0.77) in non-immunotherapy trials. There was also no statistically significant difference in OS and PFS between sexes in the rGBM cohort: median PFS was 3.6 [3.0, 4.1] months in males vs 4.1 [3.8, 5.2] months in females and median OS was 8.4 [7.4, 9.6] vs 9.6 [8.2, 12.1] months in immunotherapy trials (N=254); median PFS was 1.8 [1.7, 2.1] vs 1.9 [1.8, 2.4] months and median OS was 8.6 [7.5, 9.6] vs 8.5 [7.3, 9.6] months in non-immunotherapy trials (N=285). CONCLUSION Sex did not have a prognostic impact on survival outcomes, regardless of the treatment modality. The impact of other clinical variables such as corticosteroid use, performance status, lymphocyte counts, and tumor burden will be reported.