Treatment Breaks Research Articles

Time to Loss of Disease Control Following Guselkumab Withdrawal in Relation to Initial Speed of Response: A Post-Hoc Analysis of the VOYAGE 2 Trial

Background: Psoriasis is a chronic inflammatory skin disorder typically requiring lifelong treatment. As such, patients may occasionally need treatment breaks. Understanding factors predicting maintenance of disease control during treatment breaks could improve long-term disease management. This post-hoc analysis of data from the Phase 3 VOYAGE 2 clinical trial evaluates how initial speed of response to guselkumab treatment affects time to loss of disease control following treatment withdrawal and identifies baseline characteristics corresponding with maintenance of disease control. Methods: Patients with moderate-to-severe plaque psoriasis assigned to treatment withdrawal following achievement of a Psoriasis Area and Severity Index (PASI)90 response after two or four guselkumab doses. Loss of disease control was defined as time to PASI ≥3 and was assessed using Kaplan–Meier analysis. The relationship between baseline characteristics and maintenance of response was evaluated using a Cox proportional hazards model. Results: Of patients who were randomized to placebo and switched to guselkumab at Week 16, 149/248 (60%) achieved PASI90 after two guselkumab doses (Week 28). Of patients who were randomized to guselkumab, 377/496 (76%) achieved PASI90 after four guselkumab doses (Week 28), of whom 182 were then re-randomized to withdrawal. Of these, 131 had achieved PASI90 after two guselkumab doses (Week 12) and 51 had achieved PASI90 after four guselkumab doses (Week 28). Maintenance of disease control following guselkumab withdrawal was longer in patients who achieved PASI90 after two versus four guselkumab doses. Lower body mass index, biologic naïve status, and shorter disease duration at baseline corresponded with a longer time to PASI ≥3 following withdrawal. Conclusion: Faster initial response to guselkumab resulted in longer maintenance of disease control after treatment withdrawal. These findings may be used to inform personalized dosing strategies with guselkumab, which may increase patient compliance to treatment and improve long-term treatment outcomes.

Atypical femur fracture following romosozumab and bisphosphonate treatment.

Romosozumab, a monoclonal antibody against sclerostin, is a newly licensed dual-acting osteoporosis treatment for patients at very high risk of fracture. Sclerostin inhibition leads to stimulation of bone formation and simultaneous inhibition of bone resorption. Only three cases of atypical femur fractures were reported out of 5,621 patients who received romosozumab in the pivotal randomised controlled trials FRAME and ARCH; however, most enrolled clinical trial patients were osteoporosis treatment-naïve or had a prolonged washout period. We report a case of an atypical femur fracture that occurred after the completion of romosozumab treatment which was followed by one dose of 5 mg intravenous zoledronic acid. The patient had previously received a 2-year course of subcutaneous teriparatide and subsequent three consecutive yearly intravenous zoledronic acid infusions, followed by a 2-year treatment break. This case highlights the risks of prolonged suppression of bone resorption, which includes romosozumab due to its dual action and the need for further research on how to minimise such deleterious medication effects. Patients who are switched from prolonged antiresorptive treatment to romosozumab, should be risk-assessed and counselled for the risk of atypical femur fracture.

Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT.

Hand eczema is common and a cause of morbidity and occupational disability. When education, irritant/contact allergen avoidance, moisturisation and topical corticosteroids are insufficient to control chronic hand eczema, ultraviolet therapy or systemic immune-modifying drugs are used. There is no treatment pathway generally accepted by UK dermatologists. Compare alitretinoin and ultraviolet therapy as first-line therapy in terms of disease activity at 12 weeks post planned start of treatment. Prospective, multicentre, open-label, two-arm parallel group, adaptive randomised controlled trial with one planned interim analysis, and an economic evaluation. UK secondary care dermatology outpatient clinics. Patients with severe chronic hand eczema unresponsive to at least 4 weeks of treatment with potent topical corticosteroids. Natural logarithm of the Hand Eczema Severity Index + 1, 12 weeks post planned start of treatment. Participants randomised 1:1 by minimisation to alitretinoin or ultraviolet therapy for 12 to 24 weeks. Blinded primary end-point assessor. Intention-to-treat population: 441 (100.0%) participants; 220 (49.9%) alitretinoin and 221 (50.1%) ultraviolet therapy. At least one dose was received by 212 (96.4%) alitretinoin and 196 (88.7%) ultraviolet therapy participants. The unadjusted median (interquartile range) relative change in hand eczema severity index at 12 weeks was 30% (10-70%) of that at baseline for alitretinoin compared with 50% (20-100%) for ultraviolet therapy. There was a statistically significant benefit of alitretinoin compared with ultraviolet therapy at 12 weeks, with an estimated fold change or relative difference (95% confidence interval) = 0.66 (0.52 to 0.82), p = 0.0003 at 12 weeks. There was no evidence of a difference at 24 or 52 weeks, with the estimated fold change (95% confidence interval) equal to 0.92 (0.798 to 1.08) and 1.27 (0.97 to 1.67), respectively. Fifty-nine per cent allocated to alitretinoin and 61% allocated to ultraviolet therapy achieved a clear/almost clear assessment during the trial period. Differential treatment compliance observed: 145 (65.9%) alitretinoin and 53 (24.0%) ultraviolet therapy participants confirmed compliance (≥80% received, no treatment breaks > 7 days during first 12 weeks). High levels of missing data were observed. One hundred and thirty-five reportable adverse events across 79 participants, 55 (25.0%) alitretinoin and 24 (10.9%) ultraviolet therapy. Four serious adverse events (two alitretinoin, two ultraviolet therapy). Four pregnancies reported (three alitretinoin, one ultraviolet therapy). No new safety signals were detected. As a first-line therapy, alitretinoin showed more rapid improvement and superiority to ultraviolet therapy at week 12. This difference was not observed at later time points. Alitretinoin is cost-effective at weeks 12 and 52. Ultraviolet therapy is cost-effective after 10 years, with a high degree of uncertainty. Hand eczema severity index may be a useful primary outcome measure for hand eczema trials; ALPHA results will inform future trials. Treatment compliance was poor for ultraviolet therapy. Regular twice weekly treatment was not received by most patients. Assessment of long-term effects of randomised treatments was complicated by use of second-line treatments post treatment phase. Further analysis of substudies and pilot data will provide valuable information for future studies. A clear need for better therapeutic approaches for severe chronic hand eczema remains. Future studies will need to further address long-term benefits of treatments given. This trial is registered as ISRCTN80206075. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/186/01) and is published in full in Health Technology Assessment; Vol. 28, No. 59. See the NIHR Funding and Awards website for further award information.

Dosimetric and On-treatment Clinical Results of a Volumetric-based Skin-sparing Planning Technique for Patients Treated to the Breast and Chest Wall With Pencil-Beam Scanning Proton Therapy

PurposeThis study evaluates the hypothesis that a volumetric skin-sparing planning technique (SSPT) will reduce acute dermatitis in patients treated to the breast or chest wall (CW) with proton pencil beam scanning (PBS). MethodsIn January 2022, our center incorporated volumetric-based skin-sparing objectives in addition to skin hot-spot evaluation as a SSPT. The SSPT incorporated an objective to limit the volume of a skin evaluation structure (skin-eval) receiving 95% of the prescription dose or more (V95%Rx) to ideally <50%. We compared target coverage, robustness, skin-eval dosimetry, and acute on-treatment skin toxicity in patients treated with and without incorporation of this SSPT. Patients with skin/dermal lymphatic invasion or inflammatory breast cancer were excluded. Results84 patients who received breast/CW PBS were included (43 planned without and 41 with the SSPT). There was no difference in percentages of patients treated to the intact breast/CW/immediate CW reconstruction between groups. Mean skin-evalV95%Rx was 72% vs. 30%, p<0.0001, for those treated without versus with a SSPT. Maximum %Rx to the skin-eval volume of 0.03 cc, 0.3cc, and 1cc was higher in patients treated without versus with a SSPT (103.1% vs. 101.5%; 101.3% vs. 100.4%; and 101.8% vs. 99.7% (all p=<0.0001)), respectively. There was a small difference in the mean CTV V97.5%Rx in patients treated without versus with the SSPT (97.8% vs. 96.5%, p=0.0003). Patients planned utilizing the SSPT demonstrated reduced rates of Grade 1 breast pain at Week 2 (12% vs. 33%, p=0.0424) and Grade 2 and 3 dermatitis at Weeks 4 and 5 (Week 4 dermatitis ≥ grade 2, 18% vs. 43%, p=0.0224; Week 5 dermatitis ≥ grade 2, 45% vs. 69%, p=0.0006). There were numerically more patients requiring a treatment break or not completing the full intended prescription (4 vs. 1) in the pre-SSPT cohort. ConclusionsUse of a SSPT may reduce acute skin toxicity in breast cancer patients treated with PBS.

Lymphopenia Induced by Different Neoadjuvant Chemo-Radiotherapy Schedules in Patients with Rectal Cancer: Bone Marrow as an Organ at Risk.

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials.

Tube feeding in patients with head and neck cancer undergoing chemoradio-/radio therapy: A systematic review and meta-analysis based on the GRADE approach

ScopeThe scope of this systematic review (SR) was to determine whether a nasogastric tube (NGT) or percutaneous endoscopic gastrostomy (PEG) is a more useful supportive therapy in patients with oral cancer undergoing chemoradio-/radio therapy. MethodsFor the review, two authors searched MEDLINE, Cochrane CENTRAL and Ichushi-Web to identify clinical practice guidelines, SRs and randomised controlled trials (RCTs) according to pre-determined criteria. RevMan Web was used to combine trials and analyse the data. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation system approach. ResultsIt was not possible to perform a meta-analysis of only treatment completion based on the included RCTs; therefore, we performed a meta-analysis of treatment breaks as a surrogate outcome. A meta-analysis of potential treatment breaks, including treatment discontinuation, revealed no superiority between PEG and NGT (risk ratio=0.64 [0.23, 1.79]). A meta-analysis was conducted on two RCTs regarding the harms of infection. There does not appear to be a significant increase in the risk of infection with either PEG or NGT (risk ratio=1.18 [0.45, 3.08]). The certainty of the evidence for two outcomes was judged to be very low. Further, meta-analyses of quality of life and nutritional status were not possible because of differences in assessment methods. ConclusionWe could not determine the superiority of NGT or PEG in the supportive care of oral cancer patients who received chemoradio-/radio therapy. The effect of PEG feeding is uncertain, and it is necessary to consider indications for each case.

Treatment Outcomes and Toxicity Profiles with PORTEC-3 Trial Regimen in South Asian Cohort of High-Risk Endometrial Cancer Patients: A Single-Center Ambispective Analysis

Objectives Adjuvant chemoradiation followed by chemotherapy is the current standard of care in high-risk endometrial cancer after the PORTEC-3 trial. There is a lack of data on this treatment regimen in the South Asian patient cohort. The present study aims to assess toxicity profiles and outcomes in this cohort of patients. Materials and Methods High-risk endometrial cancer patients planned for adjuvant chemoradiation followed by chemotherapy were included. Toxicity was graded using the Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events criteria. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Survival curves were compared using the log-rank test. Cox regression analysis was done to find out the predictors of DFS. Results This study included 58 patients treated from October 2016 to August 2022. Median age was 61 years (interquartile range [IQR] 56–66), with Fédération Internationale de Gynécologie et d'Obstétrique Stages I = 26 (44.8%), II = 5 (8.6%), and III = 27 (46.6%). p53 positivity was seen in 38 (65.5%) patients. Intensity-modulated radiotherapy was used in 44 (79.3%) patients. There was no treatment discontinuation during chemoradiation. Acute Grade 2 and above toxicity during chemoradiation were diarrhea in 10 (17.2%) and hematological in 2 (3.4%). For the planned adjuvant chemotherapy in 55 patients, 51 (92.7%) completed four cycles. Grade 2 or above neuropathy was seen in 11 (20%), with 5 (9%) having persisting neuropathy at 1-year follow-up. At a median follow-up of 31 months, 15 (25.8%) patients recurred; distant = 13 and isolated para-aortic = 2. The median time to recurrence was 16 months (IQR 12–22), with 80% (12 out of 15) of recurrence within the first 2 years of follow-up. The actuarial 5-year DFS and OS were 63.8 and 76.5%, respectively. In univariate analysis, p53 positivity and lymphovascular space invasion were predictors for DFS, with p-values 0.031 and 0.027, respectively. There was no significant predictor identified in multivariate analysis. Conclusion There is good tolerance and compliance to adjuvant chemoradiation and chemotherapy in this South Asian cohort of patients with high-risk endometrial cancer, with no toxicity-related treatment breaks during radiation. The majority of the recurrences were seen at distant sites and within the first 2 years of follow-up. These findings are in line with the outcomes of the PORTEC-3 trial.

Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction

Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined. To compare HF and CF PMRT outcomes after implant-based reconstruction. This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023. Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event. The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence. Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02). In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction. ClinicalTrials.gov Identifier: NCT03422003.

Temporary treatment cessation compared with continuation of tyrosine kinase inhibitors for adults with renal cancer: the STAR non-inferiority RCT.

There is interest in using treatment breaks in oncology, to reduce toxicity without compromising efficacy. A Phase II/III multicentre, open-label, parallel-group, randomised controlled non-inferiority trial assessing treatment breaks in patients with renal cell carcinoma. Patients with locally advanced or metastatic renal cell carcinoma, starting tyrosine kinase inhibitor as first-line treatment at United Kingdom National Health Service hospitals. At trial entry, patients were randomised (1 : 1) to a drug-free interval strategy or a conventional continuation strategy. After 24 weeks of treatment with sunitinib/pazopanib, drug-free interval strategy patients took up a treatment break until disease progression with additional breaks dependent on disease response and patient choice. Conventional continuation strategy patients continued on treatment. Both trial strategies continued until treatment intolerance, disease progression on treatment, withdrawal or death. To determine if a drug-free interval strategy is non-inferior to a conventional continuation strategy in terms of the co-primary outcomes of overall survival and quality-adjusted life-years. For non-inferiority to be concluded, a margin of ≤ 7.5% in overall survival and ≤ 10% in quality-adjusted life-years was required in both intention-to-treat and per-protocol analyses. This equated to the 95% confidence interval of the estimates being above 0.812 and -0.156, respectively. Quality-adjusted life-years were calculated using the utility index of the EuroQol-5 Dimensions questionnaire. Nine hundred and twenty patients were randomised (461 conventional continuation strategy vs. 459 drug-free interval strategy) from 13 January 2012 to 12 September 2017. Trial treatment and follow-up stopped on 31 December 2020. Four hundred and eighty-eight (53.0%) patients [240 (52.1%) vs. 248 (54.0%)] continued on trial post week 24. The median treatment-break length was 87 days. Nine hundred and nineteen patients were included in the intention-to-treat analysis (461 vs. 458) and 871 patients in the per-protocol analysis (453 vs. 418). For overall survival, non-inferiority was concluded in the intention-to-treat analysis but not in the per-protocol analysis [hazard ratio (95% confidence interval) intention to treat 0.97 (0.83 to 1.12); per-protocol 0.94 (0.80 to 1.09) non-inferiority margin: 95% confidence interval ≥ 0.812, intention to treat: 0.83 > 0.812 non-inferior, per-protocol: 0.80 < 0.812 not non-inferior]. Therefore, a drug-free interval strategy was not concluded to be non-inferior to a conventional continuation strategy in terms of overall survival. For quality-adjusted life-years, non-inferiority was concluded in both the intention-to-treat and per-protocol analyses [marginal effect (95% confidence interval) intention to treat -0.05 (-0.15 to 0.05); per-protocol 0.04 (-0.14 to 0.21) non-inferiority margin: 95% confidence interval ≥ -0.156]. Therefore, a drug-free interval strategy was concluded to be non-inferior to a conventional continuation strategy in terms of quality-adjusted life-years. The main limitation of the study is the fewer than expected overall survival events, resulting in lower power for the non-inferiority comparison. Future studies should investigate treatment breaks with more contemporary treatments for renal cell carcinoma. Non-inferiority was shown for the quality-adjusted life-year end point but not for overall survival as pre-defined. Nevertheless, despite not meeting the primary end point of non-inferiority as per protocol, the study suggested that a treatment-break strategy may not meaningfully reduce life expectancy, does not reduce quality of life and has economic benefits. Although the treating clinicians' perspectives were not formally collected, the fact that clinicians recruited a large number of patients over a long period suggests support for the study and provides clear evidence that a treatment-break strategy for patients with renal cell carcinoma receiving tyrosine kinase inhibitor therapy is feasible. This trial is registered as ISRCTN06473203. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Programme (NIHR award ref: 09/91/21) and is published in full in Health Technology Assessment; Vol. 28, No. 45. See the NIHR Funding and Awards website for further award information.

Circulating Tumor DNA-Guided De-Escalation Targeted Therapy for Advanced Non−Small Cell Lung Cancer

Uninterrupted targeted therapy until disease progression or intolerable toxic effects is currently the routine therapy for advanced non-small cell lung cancer (NSCLC) involving driver gene variations. However, drug resistance is inevitable. To assess the clinical feasibility of adaptive de-escalation tyrosine kinase inhibitor (TKI) treatment guided by circulating tumor DNA (ctDNA) for achieving complete remission after local consolidative therapy (LCT) in patients with advanced NSCLC. This prospective nonrandomized controlled trial was conducted at a single center from June 3, 2020, to July 19, 2022, and included 60 patients with advanced NSCLC with driver variations without radiologically detectable disease after TKI and LCT. The median (range) follow-up time was 19.2 (3.8-29.7) months. Data analysis was conducted from December 15, 2022, to May 10, 2023. Cessation of TKI treatment and follow-up every 3 months. Treatment was restarted in patients with progressive disease (defined by the Response Evaluation Criteria in Solid Tumors 1.1 criteria), detectable ctDNA, or elevated carcinoembryonic antigen (CEA) levels, whichever manifested first, and treatment ceased if all indicators were negative during follow-up surveillance. Progression-free survival (PFS). Secondary end points were objective response rate, time to next treatment, and overall survival. Among the total study sample of 60 participants (median [range] age, 55 [21-75] years; 33 [55%] were female), the median PFS was 18.4 (95% CI, 12.6-24.2) months and the median (range) total treatment break duration was 9.1 (1.5-28.1) months. Fourteen patients (group A) remained in TKI cessation with a median (range) treatment break duration of 20.3 (6.8-28.1) months; 31 patients (group B) received retreatment owing to detectable ctDNA and/or CEA and had a median PFS of 20.2 (95% CI, 12.9-27.4) months with a median (range) total treatment break duration of 8.8 (1.5-20.6) months; and 15 patients (group C) who underwent retreatment with TKIs due to progressive disease had a median PFS of 5.5 (95% CI, 1.5-7.2) months. For all participants, the TKI retreatment response rate was 96%, the median time to next treatment was 29.3 (95% CI, 25.3-35.2) months, and the data for overall survival were immature. The findings of this nonrandomized controlled trial suggest that this adaptive de-escalation TKI strategy for patients with NSCLC is feasible in those with no lesions after LCT and a negative ctDNA test result. This might provide a de-escalation treatment strategy guided by ctDNA for the subset of patients with advanced NSCLC. ClinicalTrials.gov Identifier: NCT03046316.

Real world experience of trastuzumab deruxtecan for the treatment of metastatic breast cancer in the UK.

1024 Background: Trastuzumab deruxtecan (TDXd), an antibody drug conjugate, was first approved in the UK for the treatment of human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) in 2021. We aimed to review the efficacy and tolerability of TDXd in a real-world UK setting. Methods: We collected clinical and demographic data from medical records on HER2+ mBC patients treated with TDXd in the UK from Jan 2021 to Dec 2023 inclusive. This included: radiological response, the frequency of dose reductions and treatment delays, and reasons for discontinuation. Clinical trial patients were excluded. Descriptive statistical techniques were applied. Results: Data was collected from 26 UK cancer centres on 280 patients. The median age at TDXd initiation was 56 years (range 29-85). Median treatment duration was 9 cycles (range 1-40). 239 patients (85%) had visceral disease. 257 and 196 patients (92% and 70%, respectively) had received prior Trastuzumab and Pertuzumab, respectively. 233 patients (83%) had received prior TDM1. The median number of lines of treatment prior to TDXd was 3 (range 1 to 9). 20 patients (7%) were initiated on a reduced dose and 115 further patients (41%) required at least one dose reduction. 151 patients (54%) had at least one dose interruption due to: infection or neutropenia (n=61), other toxicity (n=85), interstitial lung disease (ILD) investigation (n=39), patient request (n=81), other concurrent illness (n=10), and cardiac investigation (n=6). Of these, 55 patients had more than one treatment break. 157 patients (56%) had discontinued TDXd treatment due to: disease progression or death (n=100), drug toxicity (n=39) of which 22 were due to ILD, and patient choice (n=8). 123 patients remained treatment at the time of analysis. The overall response rate of TDXd was 63% overall: stable disease 23%, partial response 56%, complete response 7%. Conclusions: The real-world data set is not directly comparable to either the DB02 or DB03 trials, as it included patients who had received TDXd in both the second line and later line settings. However, the majority (80%) of these patients were treated in the third line and beyond. The rates of drug interruption and reduction were higher in the real-world data set than in DB02, which may impact on efficacy in the real-world setting. Overall response rate is similar between trial data and our real-world data, although the latter was not measured by RECIST. Data collection is ongoing, including an analysis of real-world progression free survival. [Table: see text]

Pharmacodynamic (PD) and immunophenotyping analyses of ATR inhibitor (ATRi) tuvusertib + ATM inhibitor (ATMi) lartesertib in a phase Ib study in patients with advanced unresectable solid tumors.

2612 Background: Ataxia telangiectasia-mutated (ATM) and Rad3-related (ATR) protein kinases orchestrate the DNA damage response. A synthetic lethal relationship between ATR and ATM genes in cancer has been described1 and ATMi synergistically potentiate the efficacy of ATRi in vitro and in vivo.2 The combination of tuvusertib + lartesertib was investigated in Part A1 of the open-label, multicenter study DDRiver Solid Tumors 320 in patients with advanced unresectable solid tumors. Here, we report results of the PD and immunophenotyping analyses. Methods: PD analysis comprised γ-H2AX in serial blood samples, stimulated ex vivowith 4-NQO, bleomycin, or controls. Flow cytometry was used to measure target inhibition via γ-H2AX modulation in the CD45+ lymphocytes fraction and to explore the effect of tuvusertib + lartesertib on the immunophenotype (myeloid-derived suppressor cells, T and B lymphocytes, monocytes, and natural killer cells subsets) in serial blood samples. Pharmacokinetic samples were analyzed by a validated bioanalytical liquid chromatography/mass spectrometry method. Time-matched blood samples were collected at baseline, 1, 3, 6, and 24 hours after first tuvusertib and lartesertib administration on days 1 and 8 of cycle 1 for the γ-H2AX analysis, and on days 1 and 15 of cycles 1 and 2 before treatment for immunophenotyping. Results: Immunophenotyping data and γ-H2AX levels were obtained from 41 and 34 patients, respectively. For tuvusertib, complete or almost complete target inhibition was seen at 1–6 hours after treatment, followed by a rebound above baseline after 24 hours, on both days 1 and 8 at doses of 130 and 180 mg once daily (QD). For lartesertib, a variable target inhibition of approximately 50 % on average was seen across all time points at doses of 100, 150 and 200 mg QD. No target inhibition was seen for tuvusertib at 90 mg QD and lartesertib at 50 mg QD (cohort 1). Tuvusertib + lartesertib induced a transient decrease of monocytes and natural killer (NK) cells, with partial or complete recovery to baseline levels during treatment breaks in schedules of 2 weeks on treatment followed by a treatment break of 1 or 2 weeks, respectively. Conclusions: Tuvusertib and lartesertib combination PD outcomes were in line with respective monotherapy observations.3,4 The combination did not cause any consistent change in the levels of immune cell subsets at all dose levels tested, except a mild, transient decrease in monocytes and NK cells, in line with the tuvusertib monotherapy observations. 1. Kantidze et al., Trends Cancer 2018;4(11):755–68. 2. Turchick et al., Mol Cancer Ther 2023;22(7):859–72. 3. Yap et al., Ann Oncol 2022;33(suppl_7):S197–S224. 4. Siu et al., Cancer Res 2023;83(8_Suppl):CT171. Clinical trial information: NCT05396833 .

Fractionated external-beam radiation therapy in elderly patients.

e13764 Background: To review the outcome of elderly patients treated with fractionated external-beam radiation therapy (RT) at a privately-owned, multi-disciplinary cancer center. Methods: From January 7, 2019, to August 22, 2023, 63 elderly patients were treated with fractionated RT at California Cancer Associates for Research and Excellence (“cCARE”), a privately-owned, multi-disciplinary cancer center in Fresno, California. The median age at the time of RT was 90 y/o (range, 85-98 y/o). Twenty-three patients were female and 40 were male. Forty-six patients identified as white and 17 as non-white. Treatment sites/histologies included primary lung 10, non-melanomatous skin 6, bone metastases 6, breast 5, esophagus 5, H&amp;N 5, prostate 4, primary CNS 3, brain metastases 3, rectum 3, bladder 2, Merkel tumor 2, sarcoma 2, anus 1, liver 1, melanoma 1, multiple myeloma 1, NHL 1, pancreas 1 and stomach 1. Results: Thirty-two of the patients (51%) were treated with curative intent. The remaining 31 patients were treated for palliation. All patients were treated with fractionated RT. However, 4 patients also received a separate course of single-fraction RT. Twenty-seven patients received more than one course of RT. The median RT course was 10 fractions (range, 1-35 fractions). Most patients had previously been treated with systemic therapy. Nearly one third (31%) received systemic therapy concurrent with their RT. The majority of the patients (73%) completed their prescribed course(s) of RT. Many patients (61%) required one or more treatment breaks. The median duration of a treatment break was 1 day (range, 1-29 days). There were no grade 3 or higher RT toxicities recorded. The median follow-up since RT was 5 months (range, 1-59 months). Twenty-four patients have expired. The mediation duration from RT to death was 5 months (range, 1-32 months ). Of the remaining 39 patients, 92% were scored as clinically stable at the time of their last f/u visit. Conclusions: In our experience at cCARE, fractionated RT was administered to elderly patients and the majority completed their prescribed treatment courses. None of the patients in our review experienced clinically significant side effects (Grade 3 or higher) during their RT even in the cohort (31%) who were treated with concurrent systemic therapy. Clearly, careful patient selection and state-of-the-art RT administration is paramount. It is also highly advantageous for patients to be treated in a multi-disciplinary setting such as cCARE where seamless coordination of cancer care among radiation oncologists, medical oncologists and surgeons excels. A companion study is in process comparing the outcome of similarly matched elderly patients from our center who were treated with systemic therapy alone. We anxiously await the outcome of this vital comparison review.

Payor denial after prior authorization request for long-acting pain medication: Provider and patient perspectives.

11004 Background: For patients with cancer, uncontrolled pain can reduce quality of life, lead to treatment breaks, and result in worse cancer outcomes. Guideline-concordant treatment for chronic, severe pain can include long-acting opioid formulations. Pain medications, however, often face prior authorization (PA), which requires providers to obtain payor pre-approval and may result in delayed or denied care. This analysis characterizes PA-related denials for pain medications for patients with cancer. Methods: At an urban comprehensive cancer center, we identified all PA requests for outpatient long-acting opioid (i.e., buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, tapentadol) prescriptions from 2023 and described frequency of PA approvals and denials. For denials, chart review 2 weeks post-PA was conducted of provider notes and patient communications with results summarized qualitatively. Results: 1752 new long-acting opioids prescriptions for 982 unique patients required PA. Of those, 1567 (89.4%) were approved after PA process, 99 (5.6%) were denied, 81 (4.6%) were cancelled after PA initiation, and 6 (0.3%) were unresolved. Most were prescribed by pain specialists including supportive care (n = 699, 40.0%) and anesthesia/pain medicine (n = 444, 25.3%) with most common indication: “Neoplasm related pain (chronic)” (61.1%). Oxycodone was the most common long-acting opioid requiring PA (n = 551, 31.4% of prescriptions), followed by fentanyl (n = 501, 28.6%), hydromorphone (n = 205, 11.7%), and methadone (n = 137, 7.8%). Long-acting morphine was denied most frequently (16.3% of n = 129 PA requests denied), followed by buprenorphine (12.1% of n = 33), and hydromorphone (7.3%). Fentanyl was denied the least (2.8%). The 99 denials affected 62 unique patients, including a patient with 7 denials. Chart review (n = 62) of the 2 weeks post-denial revealed a median of 2 (range 0-8) provider notes mentioning pain or PA barriers and median of 1 (range 0-5) patient calls or messages about the same. 22.6% (n = 14) patients ended up in the ER or admitted to the hospital for pain crisis or failure to thrive. Providers documented poor pain control, weight loss, need to “try and fail” other medications, and noted 11.3% (n = 7) patients ending up paying out of pocket for their medications. Patient messages document uncontrolled pain and unmanageable side effects with some literally begging for relief; one patient spoke of their fear of “dying in pain”. Conclusions: The vast majority of PA requests for long-acting pain medication result in approvals, suggesting that the process -which can delay essential pain management- is largely unnecessary. For the 1 in 20 requests that were denied, provider and patient concerns highlight the negative impact of uncontrolled pain. An improved, transparent PA process is essential for adequately treating chronic, cancer-related pain.

Pharmacokinetic (PK) and pharmacodynamic (PD) findings from a phase 1b study of ATR inhibitor tuvusertib + anti-PD-L1 avelumab in patients with advanced unresectable solid tumors.

2614 Background: Ataxia telangiectasia and Rad3-related protein (ATR) kinase is critical in the DNA damage response, and its inhibition modulates antitumor immunity. The combination of ATR inhibitor (ATRi) + immune checkpoint inhibitor (ICI) has shown activity in patients with ICI-resistant tumors and may have the potential to overcome ICI resistance and induce antitumor immune responses. Methods: Part B1 of the open-label, multicenter study DDRiver Solid Tumors 320 investigated safety, tolerability, PK, and PD, including effects on immune cells, of ATRi tuvusertib in combination with the ICI avelumab (anti-PD-L1) in patients with advanced unresectable solid tumors. Flow cytometry was used to analyze tuvusertib target inhibition via γ-H2AX modulation in the CD45+ fraction of ex-vivo stimulated peripheral blood mononuclear cells, and to explore the effect on the peripheral immunophenotype. Tuvusertib PK samples were analyzed by a validated bioanalytical liquid chromatography/mass spectrometry method. Results: 22 patients were enrolled and treated with tuvusertib 180 mg once daily on a schedule of 2 weeks (w) on treatment followed by a treatment break of 1 or 2 w, and avelumab 800 mg once every 2 weeks (Q2W). The 2 w on/1 w off schedule, corresponding to the recommended dose for expansion (RDE) for tuvusertib monotherapy, was chosen for further exploration. At this schedule, 2 of 9 patients evaluable for dose-limiting toxicity (DLT) experienced DLTs: Grade 3 ALT and Grade 3 AST increase (n=1), and Grade 3 anemia requiring transfusion (n=1). A patient with chordoma experienced a RECIST v1.1 partial response. Preliminary PK data for tuvusertib suggested rapid absorption with median Tmax range of ~2–3 h and mean elimination half-life range of ~2.93 to 4.23 h, with ~2-fold accumulation of steady-state area-under-the-curve following multiple doses. Exposure of tuvusertib in combination with avelumab was consistent with tuvusertib monotherapy exposure (1). PD showed complete or almost complete target inhibition at 1–6 h after tuvusertib 180 mg followed by rebound above baseline after 24 h on days 1 and 8 of cycle 1. No clear trend of variation in absolute counts of myeloid-derived suppressor cells, T and B lymphocytes, monocytes, and natural killer cell subtypes was detected. Conclusions: Tuvusertib and avelumab were combined at established monotherapy doses with no new safety findings. Tuvusertib PD and exposure data were in line with monotherapy observations. The combination did not cause any consistent change of the immunophenotype. Given the accumulating evidence of ATRi as an immunosensitiser (2), further evaluation of this combination in patients with ICI-resistant advanced solid tumors is warranted. 1. Yap T et al., Ann Oncol 2022;33(suppl_7):S197–S224. 2. Besse B et al., JTO 2022;17(suppl_9):S41–S42. Clinical trial information: NCT05396833 .

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/μL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/μL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5k/μL, P =0.01) and larger target tumor volume (median 125 vs. 62 cm 3 , P =0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death ( P =0.04); 1-year OS rates were 63% vs 77% ( P =0.03). Receipt of photon versus proton-based RT (OR=3.50, P =0.02), higher mean liver dose (OR=1.19, P <0.01), and longer RT duration (OR=1.49, P =0.02) predicted severe lymphopenia. HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

Treatment outcome of elderly patients (≥ 78 years) with head and neck squamous cell carcinoma: A single center experience.

Patients older than the expected age of the local population generally have limited life expectancy. The optimal treatment approach for very elderly patients with head and neck cancer remains uncertain. This study retrospectively analyzed patients over 78 years old, the expected age in 2019 for Chinese individuals, who underwent treatment for head and neck cancer at a tertiary cancer center in China. The study compared the overall survival rates among different treatment groups. The findings revealed that among patients eligible for surgery, radical resection yielded better outcomes compared to radiotherapy-based treatments, with a hazard ratio of 0.362 (95% CI 0.160-0.819, P = 0.015). Among patients who received radiotherapy, those who received a total dose exceeding 60 Gy had a significantly longer survival compared to those who received palliative doses, with median survival time of 31 months versus 14 months (P = 0.003). Among 78 patients who underwent conventional fractionated radiotherapy (CFRT), 15 patients (19.23%) experienced unscheduled treatment breaks with a median duration of 12 days. However, these treatment breaks did not appear to impact survival (P > 0.1). The study also suggested that altered fractionated radiotherapy, including hypofractionated radiotherapy (hypo-RT), could be a viable alternative to CFRT, offering similar survival outcomes with reduced treatment duration. In conclusion, eligible patients should be treated with curative intent, even if they are older than the expected age of the local population. When radiotherapy is indicated, altered fractionation, particularly hypo-RT, may be a favorable option to consider.

Abstract PO4-22-04: Evaluation of acute toxicity in breast cancer patients receiving concurrent capecitabine and radiation

Abstract Purpose: Adjuvant capecitabine has been shown to improve disease-free survival and overall survival in breast cancer patients who have residual disease after neoadjuvant chemotherapy, particularly in those with triple negative breast cancer (TNBC). While adjuvant chemotherapy is often completed prior to adjuvant radiotherapy (RT), capecitabine may be administered concurrent with RT to reduce the time from surgery to RT. The purpose of this study was to evaluate the feasibility of concurrent therapy and the associated rates of acute loco-regional toxicity. Materials and Methods: A retrospective chart review was performed to identify all breast cancer patients who received adjuvant capecitabine and RT. Patients with a history of prior RT, patients who were treated with capecitabine and RT sequentially, and patients who were treated with palliative intent were excluded. Capecitabine was given Monday-Friday during RT. Patient and disease characteristics, capecitabine and RT treatment details, acute toxicity, and treatment breaks were recorded. Toxicity was scored by the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Results: A total of 27 patients with non-metastatic breast cancer who received concurrent capecitabine and RT with definitive intent treated from 2013 to 2023 were identified. Median age at diagnosis was 52 years [Interquartile Range (IQR) 40-60]. Adjuvant capecitabine dose ranged from 500-1500 mg twice daily. Adjuvant RT dose ranged from 42.56 Gray (Gy) to 50.4Gy. The majority of patients (92.6%) received a sequential 10-14 Gy boost to the lumpectomy site or mastectomy scar, and 70.3% of patients received elective regional nodal RT. During treatment, all patients developed Grade 1 or 2 radiation dermatitis, while Grade 3 radiation dermatitis was noted in 4 (14.8%) patients. Two patients required a treatment break from RT, and both patients were able to subsequently complete their planned RT course. Seven patients (25.9%) required a capecitabine dose reduction or capecitabine treatment break during RT. No Grade 4 or 5 toxicities were reported. Median follow-up from RT completion was 7 months [IQR 0.98-12.2]. At last follow-up, radiation dermatitis had improved to Grade 0-1 for all patients. Conclusion: Concurrent adjuvant capecitabine and RT is a feasible treatment approach that is well tolerated with acceptable acute toxicities. Citation Format: Ahmed Shalaby, Zohaib Sherwani, Lara Hathout, Imraan Jan, Bruce Haffty, Mridula George, Shicha Kumar, Coral Omene, Deborah Toppmeyer, Nisha Ohri. Evaluation of acute toxicity in breast cancer patients receiving concurrent capecitabine and radiation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-04.

Safety and Efficacy of Extended Therapy with [177Lu]Lu-PSMA: A German Multicenter Study.

Prospective results have demonstrated favorable safety and efficacy of [177Lu]Lu-PSMA radiopharmaceutical therapy for up to 6 cycles in men with metastatic castration-resistant prostate cancer. However, no systematic data are available outlining the feasibility of extended therapy beyond 6 cycles. We aim to evaluate the safety and efficacy of extended [177Lu]Lu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. Methods: In total, 111 patients were included in this multicenter retrospective analysis. Based on individual decisions, patients underwent uninterrupted continuation of therapy (continuous treatment) or reexposure after a therapy break (rechallenge treatment) between 2014 and 2023. Overall survival, 50% prostate-specific antigen (PSA) decline (measured 8-12 wk after treatment initiation or rechallenge), PSMA PET response, and grades per Common Terminology Criteria for Adverse Events were assessed. χ2 tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Results: Patients received extended treatment with [177Lu]Lu-PSMA, either as a continuous treatment (43/111, 38.7%) or as a rechallenge (68/111, 61.3%) treatment, with median cumulative doses of 57.4 or 60.8 GBq, respectively. Overall survival from the initiation of [177Lu]Lu-PSMA was 31.3, 23.2, and 40.2 mo for the entire cohort, the continuous treatment group, and the rechallenge treatment group, respectively. The initial 50% PSA decline was significantly higher in the retreated group than in the continuous group (57/63 [90.4%] vs. 26/42 [61.9%]; P = 0.006). A 50% PSA decline was observed in 23 of 62 patients (37.1%) after the first rechallenge. The rate of grades 3-4 toxicity was comparable between continuous and rechallenge treatments (anemia, 7/43 [16.3%] vs. 13/68 [19.1%)], P = 0.6; leukocytopenia, 1/43 [2.3%] vs. 2/67 [3.0%], P = 0.3; thrombocytopenia, 3/43 [7.0%] vs. 3/68 [4.4%], P = 0.3; renal, 2/43 [4.7%] vs. 5/68 [7.4%], P = 0.2). Conclusion: Extended therapy with [177Lu]Lu-PSMA is safe and has not been associated with increased grades 3-4 toxicity. Patient candidates for extended treatment experienced a favorable median survival of 31.3 mo from the first administration. Response under [177Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [177Lu]Lu-PSMA after a treatment break.

Abstract PO5-03-09: Concurrent versus sequential use of adjuvant capecitabine and radiation in patients with triple-negative breast cancer with residual disease: A retrospective review

Abstract Background: The CREATE-X trial demonstrated benefit of adjuvant capecitabine for patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy and surgery. In clinical practice however, physician discretion determines the sequence of capecitabine relative to radiation therapy (RT), as well as the treatment dose. Therefore, our study aimed to assess the treatment patterns and tolerance of capecitabine and RT in patients with residual TNBC at our institution after publication of the CREATE-X study. Methods: This was a retrospective IRB-approved study that included patients with TNBC who had residual disease following neoadjuvant chemotherapy and surgery and received both adjuvant loco-regional RT and capecitabine at our institution between July 1, 2017 and June 30, 2021. Patient characteristics and treatment regimens were abstracted from medical charts. For this study, we defined optimally-delivered capecitabine to be a starting dose of 1250 mg/m2 twice per day on days 1-14 every 3 weeks as per the CREATE-X trial, and all planned cycles completed without dose reductions or discontinuation. RT was defined as optimally delivered when patients completed the prescribed dose without a treatment break of &amp;gt; 1 week or discontinuation of planned RT. We used descriptive statistics to report our observations. Results: Thirty-four patients met our eligibility criteria. The median age at diagnosis was 56 years (range: 30-77 years) and the median follow up time was 48 months. Of the 27 patients who received sequential RT and capecitabine, the median starting dose of capecitabine was 1000 mg/m2. Of the 7 patients who received concomitant RT and capecitabine, the median starting dose during RT was 800 mg/m2; after completion of RT, patients completed 6 additional cycles of capecitabine at a median dose of 1000 mg/m2. We observed a greater residual breast tumor burden in patients prescribed concomitant RT and capecitabine; 71.4% were ypT2/T3 compared to only 18.5% ypT2/T3 in sequentially treated patients (OR 11.0; 95% CI, 1.64 to 73.97; p=0.05). There was no significant difference in the positive lymph node status between the 2 groups (42.9% and 40.7%, respectively). A median RT dose of 50 Gy in 25 fractions was delivered in both schedules. No patients discontinued RT due to intolerance. In the 27 sequentially treated patients, the majority (73%) received RT before capecitabine. Among these, 14 patients (51.9%) required a dose reduction and 6 patients (22.2%) discontinued capecitabine due to intolerance. Of the 7 patients receiving concomitant RT and capecitabine, 2 patients (28.5%) discontinued capecitabine due to intolerance (one during RT and one following completion of RT). The concomitant RT and capecitabine regimen was not associated with higher odds of prematurely discontinuing capecitabine compared to the sequential schedule (OR 1.15; 95% CI, 0.18 to 7.34). Conclusion: In this study, most patients received a sequential schedule and those with a higher residual disease burden were more likely to be prescribed concomitant RT and capecitabine. The starting dose of capecitabine in both schedules was lower than the starting dose in the CREATE X trial but consistent with the practice standard in the US. Our early experience did not demonstrate any signal to suggest a difference in the tolerance of capecitabine administered sequentially or concurrently. Further studies are needed to evaluate the optimal sequence of RT and capecitabine in the adjuvant setting. Citation Format: Catherine Yu, Alaina Kessler, Theresa Shao, Sarah Cate, Paula Klein, Manjeet Chadha. Concurrent versus sequential use of adjuvant capecitabine and radiation in patients with triple-negative breast cancer with residual disease: A retrospective review [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-03-09.