Price, Katharine A.

6012 Background: Up to 70% of oropharyngeal cancers in the US are reported to be HPV-mediated with most caused by HPV16 infection. First line treatment for patients with unresectable, recurrent or metastatic (R/M) disease is pembrolizumab with or without chemotherapy, but most patients eventually experience disease progression. PDS0101 is a novel, investigational HPV16-targeted immunotherapy that stimulates a potent, targeted T cell attack against HPV16-positive cancers. Methods: VERSATILE-002 (NCT04260126) is an open-label, non-randomized, Simon 2-stage study evaluating the combination of PDS0101 and pembrolizumab in subjects with HPV16-positive R/M HNSCC in 2 cohorts: ICI-naïve and ICI-refractory. All subjects receive pembrolizumab IV Q3W with PDS0101 SC administered concurrently during Cycles 1, 2, 3, 4, and 12 (max 5 doses). The primary endpoint of the study is confirmed Best Overall Response per RECIST 1.1. Herein we update the safety, PFS, and OS data for the ICI-naïve subjects. Results: Forty-eight subjects who received at least one cycle of combination therapy (safety population) had a median age of 62.5 (range 45 – 83), were 93.8% male, 93.8% White, and 62.5% ECOG 0. Among this population, the median overall treatment duration in months was 3.5 (range 0.0 – 19.5). The median number of PDS0101 doses was 4 (range 1 – 5); 56.3% received 4 doses and 22.9% received 5 doses. The median number of pembrolizumab doses was 5 (range 1 – 29); 27.1% received ≥10 doses. Efficacy was evaluated in 34 subjects (47.1% with CPS ≥20) who had assessment of tumor response following treatment (efficacy population). Tumor reduction (maximum percent change from baseline) was seen in 23 (67.6%) subjects. Nine subjects (26.5%) had confirmed response including 1 CR and 8 PR, 15 subjects had SD (44.1%), and 9 subjects had PD (26.5%). One subject was not evaluable (2.9%). The median PFS was 10.4 months (95% CI 4.2, 15.3). Among the safety population, median overall survival was non-estimable due to the ongoing survival status of study subjects. The estimated 12-month OS rate was 87.1%. Thirty-three (68.5%) subjects had mild or moderate (Grade 1 or 2) PDS0101-related TEAE (TRAE); the most common were fatigue and injection site reactions (ISRs). Only 3 subjects (6.3%) had Grade 3 TRAEs: fatigue, ISR, blood alkaline phosphatase increased, and hyperglycemia. No subjects had Grade 4 or 5 TRAE. No subject came off study due to toxicity. Conclusions: PDS0101 with pembrolizumab is well tolerated in this ICI naïve R/M HPV-associated HNSCC population. Median PFS was 10.4 months which compares favorably to published median PFS of 2-3 months for approved ICIs when used as monotherapy in patients with similar PD-L1 levels. The estimated 12-month OS of 87.1% is promising compared to published results of about 36-50%. These results justify a confirmatory randomized, controlled study. Clinical trial information: NCT04260126 .

AbstractBackgroundWe aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during, and after treatment on oncologic outcomes in human papillomavirus associated oropharyngeal cancer (HPV(+)OPSCC).MethodsRetrospective cohort at a tertiary center, 2006–2018. Multivariable Cox regressions were used to determine the effect of ALC on risk of progression. Univariate linear regression was performed to determine clinical factors associated with lower ALC.ResultsAll 197 patients underwent primary surgery. Mean (SD) ALC nadirs (×109 cells/L) were: baseline (N = 149): 1.69 (0.56); postoperative (N = 126): 1.58 (0.59); post‐RT (N = 141): 0.68 (0.35) and long‐term (N = 105): 0.88 (0.37). Lower baseline ALC nadir was associated with worse overall survival (HR 3.85, 95%CI: 1.03–14.29, p = 0.04). Lower postoperative ALC nadir was associated with higher risk of progression (HR 2.63, 95%CI: 1.04–6.67, p = 0.04).ConclusionsLower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC.Level of Evidence3

ObjectiveFailure to recognize symptoms of non‐human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV(−)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(−)OPSCC.MethodsRetrospective review at a tertiary care center. Patients with HPV(−)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care.ResultsOf 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32–127 days), with a median latency of 30 days (IQR = 12–61 days) from symptom onset to first presentation and 19.5 days (IQR = 4–46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis.ConclusionsDelays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC.Level of Evidence4 Laryngoscope, 133:1394–1401, 2023

e18544 Background: Underrepresented minority (URM) patients continue to make up a small percentage of patients treated on cancer clinical trials (CCTs), thus perpetuating health care disparities. Research indicates that engagement of healthcare staff is critical for successful recruitment. Our study sought to better define barriers to minority recruitment to CCT from the research staff perspective. Methods: Semi-structured qualitative interviews were conducted of key stakeholders for CCT enrollment, including clinical research coordinators (CRCs), principal investigators (PIs), and treating clinicians. Questions for the healthcare team explored their experiences caring for URM patients with specific inquiry into the barriers of enrollment/retention and the processes or resources required to better meet patient needs. Results: All hematology and oncology staff at Mayo Clinic Cancer Center were invited to participate via email. Of the 28 who consented, 13 were male (46%), 15 female (54%), and 21% non-white (3 Asian, 2 Hispanic, 1 Black). Of the 19 PIs, 9 were Professors (47%), 5 Associate professors (26%), and 5 Assistant professors (26%). The additional 9 interviewees were CRCs. Select themes with representative quotes and proposed actions can be seen in Table. Conclusions: Recommendations for CCT accrual include accelerating efforts to address workforce diversity gaps, engaging in community outreach, optimization of CCT participation through collaborative care, incentivizing trial participation, and creating flexibility in eligibility criteria.[Table: see text]

e18543 Background: Representation of minority patients (pts) in cancer clinical trials (CCTs) is low and contributes to health disparities. Our study sought to understand the beliefs and motivations of minority patients and to identify barriers and facilitators of CCT enrollment. Methods: 270 minority pts treated on CCT were identified from the medical record from 2018-2021. Of the 138 of pts alive, 13 (9.4%) consented. Semi-structured qualitative interviews were conducted exploring motivations, barriers, and facilitators to CCT participation. Surveys collected demographics and explored beliefs towards cancer and factors that influenced participation. Results: Of the 13 participants, 9 were female (69%), 4 Hispanic (30%), 3 Black (23%), 3 multiple races (23%), 2 Asian (15%), 2 Native American (15%), and 1 Native Hawaiian (8%). Two pts had a high school education (15%), 7 ≥ 4-year college (54%), 4 ≥ 2-year college (30%). Eight pts were married, 3 divorced, 1 widowed, and 1 single. Employment status was: employed (4 pts, 30%), unemployed (1 pt, 8%), disabled (5 pts, 38%), retired (3 pts, 23%). All pts were insured. Median household was 3 people (range 1 to > 5); 3 pts had dependents. 9 pts had their own vehicle; 4 used public or subsidized transport. 2 pts had trouble finding transportation. Income was: 3 pts < 25K, 4 pts 25-35K, 1 pts 35-50 K, 1 pts 50-75K, and 4 pts > 75K. 4 pts received emotional support from religion. All pts had heard of CCTs and 6 (46%) had known other CT participants. Direct communication from healthcare provider was the most common way of hearing about CCT. 9 pts (69%) had trust or strong trust in experimental therapy/CCT; 4 pts (30%) were neutral. 8 pts (61%) believed standard therapy was needed to cure cancer. 5 pts (38%) believed God would decide if they die from cancer. 7 pts (54%) believed that worry makes cancer worse. Key themes about patients’ motivation to participate: chance for cure, staying positive, giving back to others, having representation in research, and advancing science. Key themes about facilitators to participation: supportive family, cost coverage for treatment, and limited treatment options. Key themes on participation: minimizing logistical barriers, decentralizing CCTs, increasing awareness via patient narratives, diversifying research staff, minimizing cost, and being clear on purpose and benefit of CCT. Factors from survey that influenced participation are summarized in Table. Conclusions: Understanding minority pts experience through in-depth interviews is valuable and may help with recruitment.[Table: see text]

TPS6111 Background: Treatment options for recurrent and/or metastatic (R/M) salivary gland cancer (SGC) are limited with response rates to standard cytotoxic chemotherapy (CT) low at 10-30%, and responses to single-agent immune checkpoint inhibition (ICI) <10%. Current therapeutic agents used to treat R/M SGC have an unfavorable toxicity profile including cytotoxic CTs such as cisplatin and doxorubicin and the targeted therapy lenvatinib. Treatments with general applicability and acceptable side effect profile are urgently needed. Pemetrexed (PTX) is a multi-targeted anti-folate CT with an excellent safety and toxicity profile with promising responses reported in a case series of patients (pts) with R/M SGC (Viscuse P and Price K. Marked responses to pemetrexed chemotherapy for metastatic adenocarcinoma of the parotid gland: case series. Head Neck 2019;41(6):E99-103.). As the combination of PTX and pembrolizumab (PMB) showed enhanced responses and survival in pts with lung cancer, we hypothesize that PTX and PMB will have efficacy in pts with R/M SGC and that the combination will have improved anti-cancer activity compared with historical controls. Correlative studies on archived tissues include methylthioadenosine phosphorylase loss, PDL1 expression, and thymidylate synthase expression as potential biomarkers of response. Methods: MC200708 is a single institution (3-site), open-label, single arm phase II study of PTX and PMB in patients with R/M SGC. Pts will be treated in two cohorts: one for pts with adenoid cystic carcinoma (ACC) and the other for pts with all other types of SGC (non-ACC cohort). Eligible pts must be ≥18 years old, have a pathologically confirmed SGC that is not amenable to curative-intent therapy, ECOG 0-2, adequate organ function, and at least 1 measurable lesion by RECIST 1.1. Any number of lines of prior therapy is allowed; prior treatment with checkpoint inhibitors and/or PTX is allowed. Key exclusion criteria: serious medical co-morbidity or autoimmune disease, prior grade 3-4 adverse event (AE) or grade 2-4 lung AE with ICI, and uncontrolled brain metastases. Simon’s two-stage design will be used for each cohort separately given the expected difference in responses in pts with ACC and non-ACC. Primary endpoint is overall response rate. Secondary endpoints are progression free and overall survival and toxicity. All patients will receive the same treatment of PTX 500 mg/m2 IV + PMB 200 mg IV every 3 weeks until disease progression or treatment intolerance. Response assessments will occur every 3 cycles. Enrollment began July 2021 and 16 of the planned 45 patients (ACC cohort 9 of 20 pts, non-ACC 7 of 25) have been accrued. Clinical trial information: NCT04895735.

ObjectiveDiagnostic delay in human papillomavirus–associated oropharynx squamous cell carcinoma (HPV(+)OPSCC) is common due to nonspecific symptoms. We aim to describe the disease burden and oncologic outcomes of patients with HPV(+)OPSCC diagnosed >12 months after symptom onset.Study DesignThis is a retrospective cohort study of HPV(+)OPSCC patients receiving intent‐to‐cure treatment (including surgery ± adjuvant therapy or primary chemoradiation).Setting2006‐2016, tertiary care center.MethodsTumor stage was compared between patients with and without delayed diagnosis using χ2 tests. Kaplan‐Meier survival analysis with univariate and multivariable Cox regressions were used to determine the effect of diagnostic delay on oncologic outcomes.ResultsIn total, 664 patients were included. Compared to patients diagnosed <12 months from symptom onset (n = 601), those diagnosed at >12 months (n = 63) were more likely to have T4 disease and higher overall American Joint Committee on Cancer (AJCC) clinical stage at presentation (P <. 01 for both). At 5 years, rates of overall survival, cancer‐specific survival, progression‐free survival, and distant metastases–free survival in the delayed diagnosis cohort were 80%, 90%, 80%, and 89%, respectively. A >12‐month delay in diagnosis did not significantly impact overall survival (adjusted hazard ratio [aHR], 1.16; 95% CI, 0.58‐2.31), cancer‐specific survival (aHR, 0.83; 95% CI, 0.29‐2.39), progression‐free survival (aHR, 1.15; 95% CI, 0.56‐2.37), or distant metastases–free survival (aHR, 1.00; 95% CI, 0.42‐2.40) after adjusting for age, sex, and clinical AJCC stage (P >. 05 for all).ConclusionsDelayed diagnosis of HPV(+)OPSCC is associated with greater burden of disease at presentation, but oncologic outcomes remain favorable across treatment modalities. When appropriate, intent‐to‐cure therapy should be pursued despite diagnostic delay.Level of EvidenceLevel III.

AbstractBackgroundCutaneous squamous cell carcinomas (CSCC) involving the head and neck are common, but initial presentation or recurrence limited to the cranial nerves is rare.MethodsWe conducted a retrospective study of 21 patients with clinical perineural invasion (PNI) from CSCC and no measurable disease by RECIST 1.1. Patients treated with radiotherapy or chemoradiotherapy were included.ResultsThe median time from symptom onset until diagnosis was 13.0 months (2.6–83.1). All patients received radiotherapy. Fourteen received concurrent systemic therapy. The median follow‐up time was 30.5 months (1.1–106.0). Ten patients recurred, with the majority being locoregional. The 2‐year overall survival rate was 85%. The median progression‐free survival (PFS) was 21.5 months with an estimated 2‐year PFS of 44.5% (95%CI: 22.3–66.8).ConclusionsCSCCs with clinical PNI alone are difficult to diagnose and can have a long interval between appearance of symptoms and diagnosis. They can successfully be treated with chemoradiotherapy. However, many patients still suffer from locoregional recurrences.