Updates in Radiotherapy at ASCO 2025

ASCO 2025 isn’t just another medical conference; it’s the crucible where the future of cancer care takes shape. For five intense days in Chicago, the brightest minds in oncology converge, not to simply present data, but to spark conversations that will fundamentally alter how we diagnose, treat, and ultimately conquer cancer.

Imagine the culmination of years of dedicated research, unveiled to a global audience of clinicians and scientists. This is where breakthroughs in radiotherapy, immunotherapy, precision medicine, and novel treatment strategies are dissected, debated, and ultimately translated from promising ideas into actionable pathways for patient care. It’s a dynamic forum driven by the shared mission of pushing the boundaries of what’s possible in the fight against this complex disease.

Lutetium-177–PSMA-617

A compelling poster presentation by Nikitas et al. at ASCO 2025 unveils the rationale and design for RE-LuPSMA, a pivotal phase 2 clinical trial (NCT06288113) investigating the re-administration of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer (mCRPC) patients. Building on the established benefit of 177Lu-PSMA-617 from the VISION trial, which showed improved overall survival in previously treated mCRPC patients, this new study addresses the critical unmet need for subsequent treatment options when patients inevitably relapse.

The RE-LuPSMA trial, an investigator-initiated, single-arm, single-center, open-label study, plans to enroll 40 patients who previously achieved at least a 50% PSA decline during their initial 4-6 cycles of 177Lu-PSMA-617 therapy and subsequently progressed. Participants, who must meet specific PSMA PET/CT VISION criteria, will receive up to six additional cycles of 177Lu-PSMA-617 (7.4 GBq every 6 weeks).

The primary endpoint is 12-month overall survival from the start of re-challenge therapy, with the study powered to detect a significant difference, aiming for a 71% survival rate compared to a null hypothesis of 50%. Secondary endpoints will assess safety, PSA response rates, biochemical and radiographic progression-free survival, and health-related quality of life. Enrollment has commenced, with a projected 4-year study duration including a 12-month accrual period. While this poster focuses on the trial’s design, the anticipation for future data from RE-LuPSMA is high, as it promises to provide much-needed prospective evidence for a crucial treatment strategy in relapsed mCRPC.

Nasopharyngeal Carcinoma and Chinese Traditional Medicine

During a compelling Rapid Oral Abstract Session at ASCO 2025, Liu et al. presented findings from a large-scale, randomized, open-label, multicenter, phase IV trial evaluating Biyan Qingdu Granula (BQG) for attenuating acute radiation-induced nasal and oral injuries in nasopharyngeal carcinoma (NPC) patients. Conducted across 30 Chinese hospitals from July 2022 to May 2024 (ChiCTR2200060900), the trial randomized 1000 NPC patients (1:3) to receive either routine care (control, n=250) or routine care plus BQG (treatment, n=750). All patients received standard oral and nasal hygiene. Patients in the treatment arm took BQG twice daily throughout their 6-week radiotherapy course.

The results, with 731 BQG patients and 250 control patients completing the trial, demonstrated significant benefits. After six weeks, the incidence of severe nasopharyngeal secretion (middle or higher grade) was notably lower in the BQG group (12.4%) compared to the control group (20.0%, P=0.0033). Similarly, the incidence of severe oral mucositis (WHO grade 3 or higher) was significantly reduced in the BQG arm (12.3%) versus the control arm (22.4%, P=0.0001). While the 95% CI for the intergroup rate difference in oral mucositis (-10.1% (-15.8%, -4.4%)) narrowly missed concluding clear superiority due to the upper limit being greater than -10%, a strong trend favoring BQG was evident.

Furthermore, the BQG group exhibited a remarkable reduction in severe sore throat pharyngeal pain (VAS score) and the grade of dry and burning throat symptoms. Importantly, the incidence of adverse events was similar between both groups, highlighting BQG’s favorable safety profile in this vulnerable patient population. These findings suggest that BQG offers a valuable adjunctive treatment to mitigate challenging side effects of radiotherapy in NPC.

Read More About ASCO 2025 Updates at OncoDaily’s Website

New Insights into Dysphagia Management

Under the “Symptom Science and Palliative Care” session at ASCO 2025, Hutcheson et al. presented groundbreaking results from the PRO-ACTIVE trial (NCT03455608) in an Oral Abstract Session. This international, multi-site pragmatic phase IV randomized clinical trial tackled the critical question of optimal timing and intensity for swallowing therapy in head and neck cancer (HNC) patients undergoing radiotherapy (RT). While prophylactic swallowing interventions have gained popularity, the best approach remained uncertain. The PRO-ACTIVE trial hypothesized that proactive therapies would be more effective than reactive ones, and that a more intensive proactive regimen (EAT+EXERCISE) would surpass a less intensive one (EAT).

The study randomized 952 adult HNC patients receiving curative intent RT, predominantly those with oropharyngeal tumors (69.5%) and p16+/HPV+ disease (73.0%), all with excellent baseline swallowing function. Patients were assigned to either a RE-ACTIVE arm (weekly monitoring, therapy only if dysphagia occurred) or one of two PRO-ACTIVE arms (bi-weekly therapy pre- and during RT, either EAT or EAT+EXERCISE).

Contrary to the initial hypotheses, the trial’s findings demonstrated a surprising lack of significant difference across the groups. At 12 months post-RT, the primary endpoint of feeding tube (FT) use in days did not meaningfully differ between proactive and reactive timing (adjusted difference of 5.4 days, p=0.37) or between the EAT and EAT+EXERCISE intensities (adjusted difference of 5.9 days, p=0.21). Notably, overall FT utilization was lower than expected, with 39.1% of patients requiring an FT for a mean of 34.4 days. Secondary measures, including swallowing-related quality of life, diet, weight/BMI, and dysphagia symptoms, also showed no meaningful distinctions between the arms.

The conclusions drawn by Hutcheson et al. suggest that swallowing outcomes were favorable across all arms of the PRO-ACTIVE trial, indicating the relative effectiveness of various swallowing therapy approaches during HNC radiotherapy, irrespective of their precise timing or intensity. This pragmatic trial, being robustly powered, sets the stage for future critical analyses, including exploring heterogeneous treatment effects in subgroups and integrating image-based swallowing metrics, to further refine personalized dysphagia management strategies.

Treatment of Radiotherapy-Induced Nausea and Vomiting

In a compelling Oral Abstract Session within the “Symptom Science and Palliative Care” track at ASCO 2025, Vijayan et al. presented the definitive results of a prospective, placebo-controlled, randomized Phase III trial evaluating the role of olanzapine in reducing radiation-induced nausea and vomiting (RINV) in patients undergoing abdominal-pelvic radiotherapy. The study, conducted between February 2022 and August 2024, randomized 301 eligible patients (153 to placebo, 148 to experimental) to receive either 5mg olanzapine or a matching placebo daily, in addition to standard antiemetic care with ondansetron.

The findings unequivocally demonstrated olanzapine’s significant efficacy. During radiotherapy, a dramatic difference in reported “no nausea” was observed, with 85.8% in the olanzapine arm compared to only 16.3% in the placebo arm (p < 0.001). Similarly, “no vomiting” was reported by 95.9% of patients receiving olanzapine versus 74.5% in the placebo group (p < 0.001). The total number of vomiting episodes exceeding 15 times during RT was markedly lower in the olanzapine group (2%) compared to placebo (9.2%, p=0.002), and rescue therapy was required by only 1.4% of olanzapine patients versus 7.8% of placebo patients (p=0.008).

Moreover, the study highlighted a substantial reduction in severe RINV: Grade $\geq$2 nausea was reported by 7.4% in the olanzapine arm compared to 67% in the placebo arm (p=0.001), and Grade >/= 2 vomiting by 1.4% vs. 7.8% (p=0.001). This benefit extended across cancer types, with particularly striking results in rectal cancer patients, where Grade >/= 2 nausea was 2.8% with olanzapine versus 85.7% with placebo (p=0.001). While prostate cancer also saw a reduction (9% vs 19%, p=0.018), the effect was less pronounced than in rectal cancer.

Beyond antiemetic benefits, olanzapine positively impacted patient well-being. Anxiety scores significantly decreased post-RT in the experimental arm (from 13.4 to 11.1, p<0.001), contrasting with an increase in the placebo arm. Depression scores also improved with olanzapine (from 11.9 to 9.7, p<0.001). Patients on olanzapine reported significantly more sleep (8.4 vs. 5.29 hours/day, p<0.001) and showed improvements in emotional function, nausea/vomiting, insomnia, and loss of appetite on quality of life assessments (all p<0.001). While the mean EORTC GHS QOL score at RT completion was not statistically different between arms (62.9 vs 61.6, p=0.235), the individual symptom improvements are highly significant. Adverse reactions with olanzapine were predominantly Grade 1 and included drowsiness, dysarthria, and orthostatic hypotension.

In conclusion, Vijayan et al.’s robust data unequivocally establish that adding 5mg olanzapine to standard antiemetic regimens provides a significant and clinically meaningful reduction in RINV, along with improved anxiety, depression, sleep, and overall quality of life, for patients undergoing abdominal-pelvic radiation therapy. This offers a powerful new strategy for symptom management in this patient population.

Targeted Therapy For Glioblastomas

Under the “Central Nervous System Tumors” Oral Abstract Session at ASCO 2025, Chen et al. presented compelling interim results from a multicenter, double-blind, randomized Phase II trial (NCT04959500) evaluating the addition of anlotinib to the standard STUPP regimen for newly diagnosed glioblastoma (GBM). This study aimed to build on prior promising data for anlotinib, a multi-kinase inhibitor.

The trial randomized 153 eligible patients (77 to anlotinib, 76 to placebo) to receive either anlotinib (10 mg/day for 14 days per 21-day cycle) or placebo alongside TMZ-based chemoradiotherapy, followed by adjuvant TMZ and anlotinib/placebo until progression. Baseline characteristics were well-balanced between the two groups.

The study successfully met its primary endpoint, demonstrating a significant improvement in Independent Review Committee (IRC)-assessed progression-free survival (PFS). The median PFS was 9.89 months (95% CI 9.10, 11.56) in the anlotinib group, a substantial gain compared to 5.85 months (95% CI 3.58, 7.69) in the placebo group [HR 0.59 (95% CI 0.42, 0.85), p=0.0043]. Furthermore, the objective response rate (ORR) assessed by IRC was notably higher in the anlotinib arm at 16.88% (95% CI 9.31, 27.14) versus 5.26% (95% CI 1.45, 12.93) in the placebo group [p=0.0220].

Regarding safety, the most frequent Grade 3 or higher toxicities in the anlotinib group included thrombocytopenia (7.79% vs 1.32% in placebo), neutropenia (6.49% vs 3.95%), decreased lymphocyte count (6.49% vs 7.89%), decreased white blood cell count (6.49% vs 2.63%), and hypertension (5.19% vs 0%). The overall safety profile was deemed favorable, with a feasible treatment process.

While overall survival (OS) data is still maturing, these robust PFS and ORR results suggest that the combination of anlotinib with the STUPP regimen offers very good efficacy for patients with newly diagnosed GBM. Further molecular pathology analysis will be conducted as OS data becomes available.

Read More ASCO 2025 Abstracts on ASCO’s Official Website

Written By Aren Karapetyan, MD