Smith, Deanne

1089 Background: T-DXd has become an important treatment option in mBC and other malignancies. Interstitial lung disease/pneumonitis (ILD) occurred in 10-14% of pts in the DESTINY-Breast trials (0-2% G5 ILD), and with potential lower incidence/severity in earlier line settings (Krop et al, ASCO 2023). We previously reported the Mayo Clinic Rochester, MN experience with T-DXd related ILD in mBC (Hoppenworth et al, ASCO 2024). Here, we expand the data to include patients treated at all locations of the Mayo Clinic Enterprise. Methods: We retrospectively identified pts with mBC who received ≥1 dose of T-DXd across the Mayo Clinic enterprise (Rochester, MN; Mayo Clinic Health System locations in MN/WI; Scottsdale, AZ; and Jacksonville, FL) between July 2022-December 2023. Demographic, mBC characteristics, and pulmonary clinical variables were abstracted from the clinical records. Data were summarized using descriptive statistics. Diagnosis of ILD was determined by treating clinicians, and severity was approximated to CTCAE V5 based on clinical documentation. Results: 252 pts with mBC received T-DXd during the study period. The majority were Caucasian (86%) and female (99%) with a median age of 63. 91 pts (36%) were current/formers smokers and 97 (39%) had prior pulmonary comorbidities. The majority had HER2 low (155, 62%) and HR positive (164, 65%) mBC. 35 (14%) developed any grade ILD [G1: 6 (17%), G2: 13 (37%), G3: 3 (8.6%), G4: 3 (8.6%), G5: 10 (29%)], with 15 (43%) presenting with ≥G3. 29 (83%) presented with at least 1 symptom (cough or SOB). Among those with previous pulmonary toxicity, 4 (33%) had previous pneumonitis in the ILD cohort. The median prior lines of all therapies (including endocrine therapy) were 5, with a median of 3 prior lines of chemotherapy in both the ILD (range 1-13) and non-ILD cohorts (range 1-13). Median onset to any grade ILD was 7 cycles. 20 pts (57%) received steroids for ILD. 14 (40%) had a bronchoscopy, all had a CT chest, 16 (46%) were hospitalized, 7 (20%) were intubated and 1 (3%) had a lung biopsy. Pts with G5 ILD had a median of 3 lines of chemo and a median of 8 cycles prior to onset of ILD, compared to 3 lines of chemo and a median of 7 cycles for those with G1-4 ILD. G5 pts were all Caucasian females, 5 were former smokers, 5 were non-smokers, 1 had a history of pneumonitis. T-DXd was rechallenged in 4 pts (G1-2 ILD) without ILD recurrence. Conclusions: In this retrospective case series,14% of pts treated with T-DXd experienced any grade ILD (4% G5) which is in alignment with the rate observed in the pivotal DESTINY-Breast trials, though with higher rates of G5 toxicity. Among those with ILD, increased lines of therapy were not associated with increased risk. Further research is needed to correlate risk.

11145 Background: T-DXd is increasingly used in mBC. A T-DXd toxicity of special interest is interstitial lung disease/pneumonitis (ILD), occurring in 10-15% of pts in the DESTINY-Breast trials, and with potential lower incidence/severity in earlier line settings [Krop et al, ASCO 2023]. However, in routine practice, T-DXd may be used in pts with more heavily pre-treated mBC and previously exposed to other antibody-drug conjugates (ADC) [Premji et al SABCS 2023]. We evaluated the incidence/severity of T-DXd related ILD in mBC at Mayo Clinic. Methods: We retrospectively identified pts with mBC who received ≥1 dose of T-DXd at Mayo Clinic, Rochester, MN, between July 2022-December 2023. Demographic, mBC, and pulmonary clinical variables were abstracted from the clinical records. Data was summarized using descriptive statistics. Diagnosis of ILD was determined by treating clinicians, and severity to CTCAE V5 based on clinical documentation. Results: 77 pts with mBC received T-DXd during the study period. All were female, the majority (70, 91%) were Caucasian, and median age was 58. 53 (69%) had HER2-low mBC (37 HR+, 16 HR-) and 24 (31%) had HER2+ mBC (17 HR+, 7 HR-). 31 (40%) were active or former smokers. 11 (14%) had pulmonary comorbidities, including 6 (7.8%) with asthma, 2 (2.6%) with prior pneumonitis, and 3 (3.9%) with other pulmonary comorbidities. They had previously received a median of 1 line of endocrine therapy, and 4 lines of chemotherapy, with 20 (26%) having received another ADC. 17 (22%) developed any grade ILD [G1: 3 (4%), G2: 7 (9%), G3: 2 (3%), G4: 1 (1%), G5: 4 (5%)]. Among pts with ILD of any grade, 13 (76.5%) presented with at least 1 symptom (cough/SOB). The median number of T-DXd cycles prior to onset of any grade ILD was 6 (range 2-13), or 18 (range 6-39) weeks. 5 (29%) pts with any grade ILD received a prior ADC. Of pts with ≥G3 ILD (n=7), all were Caucasian, 2 (30%) were prior smokers, none had prior lung disease, and had received a median of 5 prior lines of chemo, with 4 (57%) having received a prior ADC. All grade ≥2 ILDs were treated with systemic steroids, and 1 also received IVIG. CT chest was used for diagnosis of all ILD. 7 pts (41%) required hospitalization, all of whom had bronchoscopy, with 5 (29%) requiring intubation. All pts with G1 ILD (3, 18%) restarted T-DXd without ILD recurrence. Conclusions: In this case series,22% of ps treated with T-DXd experienced ILD (5% G5), higher than the rate observed in the pivotal DESTINY-Breast trials, possibly due to real-world use of T-DXd in more heavily pre-treated pts and in pts with pulmonary comorbidities.

Abstract Background: SPPADE symptoms (Sleep disturbance, Pain, Physical function impairment, Anxiety, Depression/distress, and Energy deficits/fatigue) may result from cancer and its treatment. The aim of this analysis was to characterize SPPADE symptoms in patients with breast cancer. Methods. SPPADE data were drawn from the Enhanced, EHR-facilitated Cancer Symptom Control (E2C2) study, a stepped-wedge pragmatic cluster-randomized trial designed to evaluate a symptom management intervention in routine practice (NCT03892967). Symptom severity was measured on a 0-10 scale via a survey administered by patient portal, in-clinic tablet, or interactive voice response system (by phone) prior to, during, or soon after an outpatient oncology encounter. Scores of 4-6 were categorized as “moderate” and ≥7 as “severe.” In this analysis, only the data from each patient’s initial survey were included. Results. A total of 9,651 patients with breast cancer completed an initial E2C2 survey between March 2019 and January 2023. The proportion of patients with moderate or severe SPPADE symptoms were as follows: 22% moderate and 10% severe for insomnia; 18% moderate and 7% severe for pain; 17% moderate and 7% severe for anxiety; 15% moderate and 5% severe for emotional distress; 25% moderate and 12% severe for fatigue; and 22% moderate and 8% severe for impaired physical function. Table 1 presents score means and standard deviations by demographic subgroup. Conclusions. SPPADE symptoms are common in patients with breast cancer. These observations warrant routine implementation of symptom surveillance and management in breast oncology. Funding acknowledgement: The Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium is a Cancer Moonshot Research Initiative under the authorization of the 2016 United States 21st Century Cures Act. This research was supported by the National Cancer Institute of the NIH, UM1CA233033 (Mayo Clinic, Rochester, MN). Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer Citation Format: Kathryn Ruddy, Veronica Grzegorczyk, Deirdre Pachman, Sandra Mitchell, Bolun Liu, Deanne Smith, Ciara O'Sullivan, Shawna Ehlers, Jeph Herrin, Parvez Rahman, Andrea Cheville. Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer [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 PO2-12-09.

12114 Background: A retrospective study suggested a potential benefit from rose geranium in sesame oil nasal spray for alleviating nasal vestibulitis symptoms in patients (pts) undergoing chemotherapy. Methods: Pts undergoing active chemotherapy who reported moderate or worse nasal symptoms were randomized 1:1 to receive a rose geranium in sesame oil nasal spray (RG) or an isotonic saline nasal spray (IS), administered twice daily for two weeks. Consenting pts completed nasal symptom questionnaires at baseline and then weekly while on treatment. The number and percentage of pts experiencing improvements in their nasal symptoms 2 weeks after initiating the nasal spray, defined as symptoms moderately (2) or very much (3) better on a 7-point global impression of change score (ranging from scores of -3: very much worse, to 3: very much better), was estimated within and then between each randomized arm, using Fisher’s exact test (5% significance level). The estimated odds ratio was determined (95% confidence interval). After 2 weeks, pts initially randomized to IS were allowed to cross-over to RG and completed weekly surveys. Results: 106 pts consented to this study; 43 pts in the RG arm and 41 in the IS arm were evaluable for the primary endpoint. Pts had a mean age of 57.8 (SD 13.9). Demographic characteristics and baseline nasal symptoms were similar between arms. The most prominent baseline nasal symptoms were dryness (36%) and bleeding (35%). Of the 43 evaluable pts who received RG, 67.4% reported improved nasal symptoms, compared with 36.6% of the 41 pts who received IS (p=0.009; Table). On the global impression of change score, pts who received RG had a mean score of 1.93 (SD 1.16), compared to a mean score of 0.98 (SD 1.41) among pts who received IS. Adjusting for potential confounding factors, pts who received RG had a 4.56 odds of responding to the nasal spray, compared with those who received IS (p=0.005). There were no significant differences between pt responses based upon type of nasal symptoms, age, allergies, or gender. Adverse events were sparse and did not differ between arms. 34 pts crossed over to RG after week 2. Among the 29 pts who completed final surveys, 37% reported a response on IS, 79% reported a response on RG. Conclusions: Rose geranium in sesame oil nasal spray significantly improves nasal vestibulitis symptoms among patients undergoing chemotherapy. Clinical trial information: NCT04620369 . [Table: see text]

AbstractIntroductionNasal symptoms are frequently reported by patients undergoing chemotherapy.MethodsEligible patients planning to receive paclitaxel, docetaxel, nab‐paclitaxel, bevacizumab without a concomitant taxane, or “other” (non‐taxane, non‐bevacizumab) chemotherapy regimens were invited to participate in this prospective study. Patients reported nasal symptoms prior to each dose of chemotherapy.ResultsThe percentage of patients (95% CI) who reported nasal symptoms was the same for patients who received bevacizumab or nab‐paclitaxel, 82.6% (61.2%, 95.1%). There were no significant differences among the proportions of patients experiencing nasal symptoms within the paclitaxel, nab‐paclitaxel, and bevacizumab cohorts. Patients in the nab‐paclitaxel cohort were more likely to experience symptoms than those in the non‐taxane non‐bevacizumab cohort or docetaxel cohort (p = 0.001, p = 0.001). Patients in the bevacizumab cohort were more likely to experience nasal symptoms than those in the non‐taxane non‐bevacizumab cohort (p = 0.03).ConclusionNasal vestibulitis symptoms are common in patients receiving chemotherapy, especially those receiving paclitaxel, docetaxel, and bevacizumab. Further investigations into treatments of this symptom complex are warranted.

Abstract Purpose: Blood-based candidate biomarkers of disease can be monitored by analyzing CTCs and/or circulating cfDNA isolated from the peripheral blood. Our primary objective is to understand the relative contributions of these circulating factors (i.e., CTCs and cfDNA) to the overall disease profile in MBC. Methods: Clinically archived FFPE tumor tissue and prospective blood samples are collected through a minimal risk protocol approved by the Mayo Clinic IRB (#16-001540) from patients with MBC and objective evidence of disease progression. Blood samples include 20 mL whole blood in Streck blood collection tubes (BCTs) for platelet poor plasma (PPP); 20 mL whole blood in AccuCyte BCTs for CTCs, WBCs, and PPP; and 10 mL whole blood in EDTA BCTs for PPP. Nucleated, EpCAM+/cytokeratin+/CD45- CTCs are identified, assessed for ER/HER2 status, and isolated using a centrifugation and direct imaging platform that allows for single cell retrieval (RareCyte). DNA is extracted from PPP, CTCs, WBCs, and FFPE tumor tissue using established methods. Targeted sequencing for SNVs/indels is performed on paired WBCs and CTC-DNA, AccuCyte-cfDNA, Streck-cfDNA, EDTA-cfDNA, and tumor tissue derived DNA using the same NGS panel and informatics pipeline (65 genes; CleanPlex OncoZoom; Paragon Genomics). Results: Tissue and blood samples were collected from 40 patients with metastatic breast cancer. 10 cases were selected for initial analyses on the basis of CTC yield (range 3-113 per 3.75 mL blood); up to 5 CTCs per subject were isolated and pooled for DNA extraction. Plasma cfDNA yields and variant allele frequencies were highly comparable between AccuCyte and Streck collected blood samples. Mutations (range 1-3) were identified in CTC-DNA and/or cfDNA in 9 of 10 cases for a total of 18 detected mutations: 10 in CTC-DNA and cfDNA (BRCA2 N372H, PIK3CA E542K, PIK3CA E545K (x3), PIK3CA H1047R, PTEN R130P, RET G691S, TP53 C135W, TP53 Q192*); 5 in CTC-DNA only (EGFR R521K, EGFR T790M, PIK3CA H1047R, SMAD4 C363Y, TP53 N263D); and 3 in cfDNA only (DNMT3A W893S, DNMT3A S714C, TP53 Q136E). Parallel analyses of samples from 10 more subjects are in progress. Analysis of tumor tissue for all 20 subjects and of EDTA-cfDNA and single CTCs for a subset of cases is ongoing. Updated results will be presented at the meeting. Conclusions: It is feasible to isolate high quality CTCs and cfDNA from the same blood collection tube to perform targeted sequencing; this streamlines specimen processing, decreases overall costs, and minimizes required blood volumes. Importantly, there is overlap in the majority of mutations identified in CTC-DNA and cfDNA, but actionable mutations (e.g., PIK3CA, EGFR) were detected in CTC-DNA only. The clinical and theranostic relevance of these findings is unclear and warrants further investigation. Citation Format: Minetta C. Liu, Karthik V. Giridhar, Roberto A. Leon Ferre, Jamie L. Carroll, Matthew P. Goetz, Tufia C. Haddad, Deanne R. Smith, Siddhartha Yadav, Vidushi Kapoor, Guoying Liu, Tad George, Nolan Ericson, Arturo B. Ramirez, Eric Kaldjian, Keegan E. Haselkorn. Comparison of circulating tumor cell (CTC) derived DNA and circulating cell-free DNA (cfDNA) from simultaneous blood sampling of patients with metastatic breast cancer (MBC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3119.

9116 Background: Hot flashes affect 75 % to 90 % of women transitioning to menopause and are a major cause of morbidity among breast cancer survivors. Levetiracetam, a popular anticonvulsant, is a centrally active agent that anecdotally appeared to reduce hot flashes in clinical practice. This phase II trial sought to evaluate the efficacy of levetiracetam in reducing hot flashes among women with a history of breast cancer or women who did not wish to take estrogen therapy for fear of an increased risk of breast cancer. Methods: Women who were experiencing bothersome hot flashes (≥ 14 times per week, for ≥ 1 month) were eligible. A single arm pilot study design based on previous work was used with a planned sample size of 30 patients. The patients did not receive any study medication during the first week (baseline week). At the beginning of the second week, patients were started on levetiracetam (500 mg), and were to increase the dose by 500 mg each week to a goal of 1,000 mg twice daily. Hot flash diaries were completed daily. The primary endpoint was hot flash score (frequency times average severity). The change from week 1 (baseline) to week 5, the last treatment week, was analyzed by paired t-test and related Wilcoxon procedures. Results: A total of 30 women were enrolled onto this study in eight months. All patients were eligible. 19 women completed all 4 weeks of the study treatment and provided complete data. After treatment with levetiracetam for 4 weeks, mean hot flash scores were reduced by 57% (95% CI 39%-75%), while mean hot flash frequencies were reduced by 53% (95% CI 38%-68%), reductions being greater than what would be expected with a placebo. There were significant improvements, compared to baseline week data, in sweating, hot flash distress, and satisfaction with hot flash control. Eight subjects stopped the study drug due to treatment related adverse events (grade I/II), with the most frequently reported being somnolence, fatigue and dizziness. Conclusions: While levetiracetam appears to be a promising therapy for the treatment of hot flashes, further study is needed to better substantiate the toxicity and efficacy of this drug before it can be more definitively recommended for use in clinical practice. No significant financial relationships to disclose.

219 Background: Dryness, crusting, and bleeding of the nares due to inflammation, termed nasal vestibulitis (NV), is infrequently reported as a side effect of cancer treatments. However, one study described 115 patients who developed NV while undergoing targeted therapies; many were treated with bacitracin ointment (Ruiz et al Sup Care Cancer 2015). Methods: This study surveyed 94 patients regarding the presence of nasal symptoms during cancer treatments. Participants were consented for the study if they had undergone at least 6 weeks of cancer-directed therapy in the Mayo Clinic Chemotherapy Unit. They were asked about types of nasal symptoms, severity, and symptom treatments. A chart review was then conducted to determine documentation of symptoms, the presence of concurrent illnesses, and cancer treatment regimens. Results: Ninety-four patients completed questionnaires, with 41% reporting unpleasant nasal symptoms that they attributed to cancer treatments. Of the symptomatic patients, 46% had dryness, 33% had discomfort, 54% had bleeding, and 46% had scabbing. Average severity was 1.9 on a scale from 1 to 3 (1 = mild, 3 = severe). Symptoms were noted in patients undergoing a variety of cancer treatment regimens, with the highest frequency in patients undergoing a taxane-containing regimen (46%). 62% of patients with symptoms said they reported them to their provider, but only 41% of chart notes (for 16 patients) contained documentation of such, most frequently described as “allergies” or “epistaxis.” Only 10% of symptomatic patients had nasal swabs; all of which were obtained during respiratory illness or pre-op. 49% of patients with nasal symptoms reported treating their symptoms. Antihistamines (7 patients), nasal saline (6 patients), or nasal lubricants (i.e. Vaseline; 7 patients) were used; 2 patients applied bacitracin. 18% of symptomatic patients had providers who recommended treatments, including 2 patients who were thought to have concurrent infection and were treated with antibiotics. Conclusions: NV symptoms are prevalent among oncology patients, but infrequently recorded or treated by providers.