Anti-programmed cell death receptor-1 (PD-1) therapy is standard of care for incurable recurrent or metastatic non-nasopharyngeal head and neck cancer. In contrast, there are no regulatory agency-approved anti-PD-1 agents indicated for the treatment of recurrent or metastatic nasopharyngeal carcinomas (RM-NPC) in the Western hemisphere, and no standard treatment option exists beyond first-line chemotherapy for RM-NPC. The pace of development of novel systemic therapy regimens for RM-NPC has been slow compared to many other advanced tumor types, leaving an unmet clinical need for these patients with a poor prognosis. Recent clinical trials have documented the clinical activity of anti-PD-1 therapy in RM-NPC. In particular, randomized clinical trials in the first-line setting have demonstrated significant improvements in progression-free survival (PFS) with the addition of anti-PD-1 therapy to standard chemotherapy. Whether the observed PFS benefits require combination chemoimmunotherapy or can be achieved with chemotherapy followed by crossover to immunotherapy upon progression remains unknown. Ongoing clinical trials are exploring novel anti-PD-1 therapy-based combinations, which may further solidify a role for these agents in RM-NPC. Among patients with RM-NPC, anti-PD-1 therapy added to first-line standard-of-care gemcitabine plus cisplatin provides significantly better efficacy outcomes compared to chemotherapy alone, and anti-PD-1 monotherapy appears to have comparable clinical activity and better tolerability than chemotherapy in previously treated disease. Thus, anti-PD-1 therapy is poised to advance standard of care for the treatment of RM-NPC.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE: To provide evidence-based recommendations for the use of transoral robotic surgery (TORS) in the multidisciplinary management of oropharyngeal squamous cell cancer (OPC). METHODS: ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. The literature search included studies published between January 1, 2002, and August 31, 2024, and comprised systematic reviews, meta-analyses, randomized controlled trials, and observational studies. Outcomes of interest include overall and disease-free survival, functional outcomes, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: A total of 58 publications were identified to inform the evidence base for this guideline. RECOMMENDATIONS: Evidence-based recommendations address the evaluation and workup of patients with human papillomavirus (HPV)–positive OPC, the role of TORS, patient selection, adjuvant therapy, HPV-negative OPC, and use of TORS in salvage or recurrent setting. Additional information is available at www.asco.org/head-neck-cancer-guidelines .

Background: Rearranged during transfection ( RET ) alterations are targetable oncogenic drivers in thyroid cancer. Primary data from the open-label, phase 1/2 ARROW study demonstrated clinical activity and manageable safety with pralsetinib, a selective RET inhibitor, in patients with advanced/metastatic RET -altered thyroid cancer. We present an updated analysis with more patients and longer follow-up. Methods: Adult patients with advanced/metastatic RET -mutant medullary thyroid cancer (MTC) or RET fusion-positive thyroid cancer who initiated oral pralsetinib at 400 mg once daily were included. Primary endpoints were overall response rate (ORR) by blinded independent central review (per RECIST v1.1) and safety. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), and overall survival. Responses were assessed in three cohorts of patients with baseline measurable disease: patients with RET -mutant MTC who had received prior cabozantinib and/or vandetanib (C/V), treatment-naïve patients with RET -mutant MTC, and patients with previously treated RET fusion-positive thyroid cancer. Patient-reported outcomes (PROs) were an exploratory endpoint. Results: As of October 18, 2021, the measurable disease population comprised of 61 patients with RET -mutant MTC and prior C/V, 62 treatment-naïve patients with RET -mutant MTC, and 22 patients with RET fusion-positive thyroid cancer who had received prior systemic therapy, including radioactive iodine. The ORR was 55.7% [confidence interval; 95% CI: 42.4–68.5] in patients with RET -mutant MTC and prior C/V, 77.4% [95% CI: 65.0–87.1] in treatment-naïve patients with RET -mutant MTC, and 90.9% [95% CI: 70.8–98.9] in patients with previously treated RET fusion-positive thyroid cancer. Median DoR and median PFS were both 25.8 months in patients with RET -mutant MTC and prior C/V, not reached in treatment-naïve patients with RET -mutant MTC, and 23.6 and 25.4 months, respectively, in patients with previously treated RET fusion-positive thyroid cancer. In the RET -altered thyroid cancer safety population ( N = 175), 97.1% of patients reported a treatment-related adverse event (TRAE); these led to discontinuation in 5.7% and dose reduction in 52.6% of patients. There was one death (0.6%) due to a TRAE. PROs improved or remained stable after pralsetinib treatment. Conclusions: In this updated analysis of the ARROW study, pralsetinib continued to show deep and durable clinical activity and a manageable safety profile in patients with advanced/metastatic RET- altered thyroid cancer. Clinical Trial Registration: NCT03037385

PURPOSE: The androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC. METHODS: Patients with locally advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in ≥ 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety. RESULTS: Forty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease ≥ 6 months. Tumor regressions were observed in female patients (5 of 6 [83.3%]) and those who received prior AR– (6 of 13 [46.2%]) or human epidermal growth factor receptor 2–targeted therapies (5 of 8 [62.5%]). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide. CONCLUSION: Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.