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Wearable-captured physiological metrics and electronic patient reported outcomes (ePROs) demonstrated feasibility at a high data completeness level in patients with Waldenström macroglobulinemia, according to findings presented during the 

Patients with Waldenström macroglobulinemia included in the study (n = 79) completed daily ePROs at a rate of 60% over a 142-day snapshot; wearable activity and sleep metrics had a completion rate of 85%. The mean EQ-5D-5L score for the entire cohort of patients was 0.760 (SD ± 0.181) and the mean Health State score was 74 (SD ± 18).

The highest mean symptom severity scores on a scale of 1 to 5 reported were fatigue (1.9), weakness (1.7), and numbness/tingling (1.5). Notably, all other symptoms examined had a mean score of 1.4 or less, including breathlessness (1.4), difficulty concentrating/confusion (1.4), vision (1.3), rash (1.2), night sweats (1.2), dizziness/lightheadedness (1.2), constipation (1.2), loss of appetite, (1.2), and diarrhea (1.1). The score of 1 represented no problems and 2 described slight problems reported.

“Waldenström macroglobulinemia is a rare hematological malignancy that has seen the emergence of novel targeted therapies,” Shirley D’Sa, MD, FRCP, FRCPath, said during the presentation. “The condition has a range of clinical features that may significantly impact quality of life and functionality for patients. Current measures of quality of life have limited validity in Waldenström macroglobulinemia, as published by our group recently, [highlighting] an urgent need for disease-specific PROs.”

D’Sa is a consultant hematologist and the clinical lead for the University College London Hospitals Centre for Waldenström’s macroglobulinemia and associated disorders. She is also an honorary associate professor at the University College London Cancer Institute and haematological lead in the joint neurohaematology service at the National Hospital for Neurology in Queen Square, London.

The study examined findings collected via an FDA-cleared wearable smartwatch—which captured activity, sleep, and heart rate data—and a mobile app where patients self-reported daily ePROs. ePROs consisted of treatments received, EQ-5D-5L scores, and disease symptoms, including fatigue, weakness, numbness/tingling, breathlessness, difficulty concentrating/confusion, vision, rash, night sweats, dizziness or light-headedness, constipation, loss of appetite, diarrhea, and vomiting. The results were integrated into a digital platform and anonymized extracts were evaluated both as a cohort and by treatment.

The study objective was to enrich the understanding of the patient experience and to identify potential Waldenström macroglobulinemia-specific metrics via wearable-captured physiological metrics and ePROs. Patients enrolled were a mean age of 65 years (SD ± 10) and most were female (53%). The most recent self-reported treatment entry was prior BTK inhibitor use (22%).

Additional findings from a correlation analysis revealed that increasing activity levels significantly correlated with decreasing symptom severity and increasing quality of life scores (

 < .05). A correlation was also reported between lower symptom severity and higher total sleep durations. However, increased difficulty concentrating/confusion, dizziness/light-headedness, and usual activity impairment scores were correlated with increased levels of deep sleep.

Subgroup analysis showed that there were no statistically significant differences between age groups; differences were only present in terms of HR zones among sex subgroups. According to data collected by the wearables, patients who received BTK inhibitors experienced higher breathing disturbance intensities compared with the overall cohort, at 36.8 vs 17.6 (

 = .008), respectively, where 0 to 29 was considered a low score, 30 to 59 was medium, and 60-plus was high. Nightly wakeup counts were also elevated among patients who received BTK inhibitors vs the overall cohort, at 1.9 vs 1.6 (

“Our primary and preliminary data support the enrichment of knowledge around baseline physiological and quality of life metrics in Waldenström macroglobulinemia,” D’Sa said in conclusion. “We will further be expanding [our research] through a larger cohort [of patients] and greater depth of health event, complications, and therapeutic intervention impact insights.”

Summers K, Agrippa O, D’Sa S. New approaches to active monitoring: Patient-reported outcomes and wearables utilisation in Waldenstrom macroglobulinemia. 

. 2024;42(suppl 23):168. doi:10.1200/JCO.2024.42.23_suppl.168

Wearable-captured physiological metrics and electronic patient reported outcomes were practical and generated knowledge in Waldenström macroglobulinemia.

Wearable-Captured Metrics and ePROs Prove Feasible as Digital Ecosystem in Waldenström Macroglobulinemia

Although overall survival (OS) and progression-free survival (PFS) benefits observed with atezolizumab (Tecentriq) plus bevacizumab (Avastin) are greater in patients with hepatocellular carcinoma (HCC) who have Child-Pugh A liver function, the combination remains an option for patients with Child-Pugh B7 liver function, according to data from a multi-institutional cohort study presented at the 

 Additional findings from the study, which were presented by Amit Mahipal, MPH, MBBS, revealed that responses rates appear similar in those with Child-Pugh A and Child-Pugh B7 liver function.

The median OS was 21.6 months (95% CI, 17.7-34.9) among patients with Child-Pugh A liver function (n = 226) treated with atezolizumab plus bevacizumab compared with 6.4 months (95% CI, 5.2-9.0) for those with Child-Pugh B liver function (n = 86) and 2.5 months (95% CI, 0.4-not evaluable [NE]) for patients with Child-Pugh C liver function (n = 10). The respective 12-month OS rates were 69.3% vs 32.4% vs 10.0%. The median PFS was 8.9 months (95% CI, 6.8-11.0) vs 4.8 months (95% CI, 2.7-6.7) vs 2.5 months (95% CI, 0.4-NE), respectively.

Additionally, 45.7% of patients with Child-Pugh B7 liver function (n = 49) were alive at 12 months. Upon further OS examination by Child-Pugh B class, patients treated with atezolizumab plus bevacizumab with B7 liver function experienced a median OS of 9.1 months (95% CI, 6.4-14.9) vs 4.7 months (95% CI, 2.6-6.1) among those with Child-Pugh B8 to B12 disease (n = 47). The median PFS was 6.4 (95% CI, 4.6-11.6) months vs 2.7 months (95% CI, 1.8-4.9), respectively. 

“Outcomes in Child-Pugh B7 [class disease] are significantly different than Child-Pugh B8 or B9 [class disease],” Mahipal, the Ruth and Donald Goodman Chair in GI Oncology at UH Seidman Cancer Center in Ohio, and coauthors noted.

Mahipal and coauthors added that atezolizumab plus bevacizumab is the preferred first-line treatment option for patients with advanced HCC based on data from the phase 3 IMBrave150 trial (NCT03434379). Although findings revealed patients treated with the combination therapy experienced improved OS compared with sorafenib (Nexavar), the trial only enrolled patients with Child-Pugh A liver function.

Therefore, this multi-institutional cohort study was conducted with the primary objective of comparing OS outcomes in patients with advanced HCC who had Child-Pugh A vs Child-Pugh B liver function; a focus was also placed on evaluating the regimen in those with Child-Pugh B7 liver function. Secondary objectives included comparing PFS, response rates, and adverse effects (AEs) among different Child-Pugh score groups.

The multi-institutional retrospective analysis included data from patients treated at University Hospitals Seidman Cancer Center and Mayo Clinic. The study took place at over 20 centers of academic and community-based practices in Minnesota, Wisconsin, Ohio, Arizona, and Florida. Patients with advanced HCC who were not amendable to receive locoregional therapy and who intended to receive atezolizumab plus bevacizumab as first-line systemic therapy were included in the analysis.

Baseline patient characteristics were generally well balanced between those with Child-Pugh A and Child-Pugh B liver function. The median age at diagnosis was 66.5 years (IQR, 61.0-72.0) among all patients in the study (n = 322); most patients were male (78.6%) and White (82.6%). Additionally, most patients did not have macrovascular invasion (57.1%), extrahepatic metastasis (69.6%), hepatitis B (94.7%), or hepatitis C (65.2%). Mahipal noted that macrovascular invasion was a bit higher in those with Child-Pugh B liver function at 52.3% vs 38.5% for those with Child-Pugh A liver function.

Further data from the trial revealed that patients with Child-Pugh A (4.4%), B (1.2%), and B7 (2.0%) liver function achieved complete responses, but those with B8-9 (n = 37) or C liver function did not. Partial responses were observed in those with a Child-Pugh liver function of A (29.2%), B (19.8%), B7 (30.6%), B8-9 (5.4%), and C (10.0%). Disease progression occurred in 28.3% vs 43.0% vs 30.6% vs 59.5% vs 50.0% of patients, respectively.

Regarding safety, immune-related AEs occurred in 15.0% of patients with a Child-Pugh A class disease and 18.6% of patients with a Child-Pugh B class disease. Fatigue occurred in 61.1% vs 61.6% of patients, and bleeding in 10.2% vs 16.3%, respectively; notably, bleeding AEs were grade 3 or higher in 11.3% of patients with Child-Pugh B liver function. Grade 1 (12.4% vs 10.5%), 2 (5.3% vs 2.3%), 3 (4.4% vs 1.2%), and 4 (0.4% vs 0.0%) hypertension also occurred in patients with Child-Pugh A and B liver function, respectively. Two patients with Child-Pugh A liver function experienced a grade 5 immune-related AE.

“[There was] no increase in rates or severity of immune-related AEs in patients with Child-Pugh B [liver function and] no significant higher risk of bleeding,” Mahipal and coauthors concluded.

Mahipal A, Zemla TJ, Patell K, et al. Multiinstitutional cohort study of patient outcomes in Child-Pugh (CP) B liver function treated with atezolizumab plus bevacizumab (A+B) for hepatocellular carcinoma (HCC). 

. 2024;42(suppl 23):50. doi:10.1200/JCO.2024.42.23_suppl.50

Finn RS, Qin S, Ikeda M, et al; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. 

. 2020;382(20):1894-1905. doi:10.1056/NEJMoa1915745

Atezolizumab plus bevacizumab showed efficacy in patients with hepatocellular carcinoma who had Child-Pugh B7 liver function.

Atezolizumab/Bevacizumab Represents Potential Therapeutic Option in Child-Pugh B7 HCC 

Patients with select rare breast cancer subtypes, such as metaplastic and lobular histologies, achieved high pathologic complete response (pCR) rates with response-predictive subtype (RPS)–optimized treatment with a checkpoint inhibitor, although patients with rare breast cancers overall experienced shorter event-free survival (EFS) vs those with no special type (NST), according to data from an analysis of the I-SPY 2 study (NCT01042379).

 showed pCR rates of 34% and 20% for patients with NST (n = 1974) and rare breast tumors (n = 142), respectively. Rare tumor histologies included metaplastic (n = 59), lobular (n = 55), mucinous (n = 9), micropapillary (n = 8), neuroendocrine (n = 4), and apocrine (n = 4). pCR rates were 27%, 15%, 0%, 25%, 0%, and 50% for these respective subtypes. Other uncommon histologies were also noted.

Further assessment of pCR according to RPS showed high response rates in the HER2-Immune+ ([S3]; NST group, 49%; rare tumor group, 39%) and HER2+ non-luminal ([S5]; 59%; 90%) subtypes. pCR rates were also observed for patients with HR+HER2-negative-Immune-DRD ([S1]; NST group, 10%; rare tumor group, 0%), HR-HER2–Immune-DRD ([S2]; 14%; 0%), HER2+luminal ([S6]; 18%; 0%), and unknown (13%; 33%) subtypes. Notably, a pCR was achieved by 56% of patients with rare tumors in the S3 immune-positive group who received RPS-optimized therapy with an immune checkpoint inhibitor (n = 18). This included 8 patients with metaplastic tumors, 1 patient with a lobular tumor, and 1 patient with an apocrine tumor.

Patients with metaplastic breast cancer in the rare tumor group had a pCR of 27% vs 34% in the NST group. Importantly, pCR rates were higher among patients treated with checkpoint inhibitors (rare tumor group, 37%; NST group, 34%) vs without (32%; 18%). For those with S3 disease who received a checkpoint blockade, there was no statistically significant difference in the pCR rate between the NST group (64%) and the rare tumor group (57%; 

“We observed high pCR rates in [patients with] metaplastic breast cancer amongst subsets of often difficult-to-treat breast cancer subtypes. This supports novel approaches and provides a roadmap for future study of rare breast cancers,” lead study author Alexandra Thomas, MD, FACP, a professor of medicine at Duke Cancer Institute in Durham, North Carolina, stated in an oral presentation of the data. “Outcomes were also improved when therapy matched RPS vulnerabilities.”

I-SPY 2 is a neoadjuvant platform designed to evaluate novel agents in combination with standard chemotherapy for patients with early-stage, high-risk breast cancer. This trial is particularly significant for patients with uncommon histologies, which are over-represented among high-risk breast cancer cases and represent an area of unmet medical need due to limited trial data. The trial uses a combination of tumor molecular signature and receptor status to determine RPS.

The study enrolled patients 18 years of age or older with high-risk, HER2-positive, triple-negative breast cancer (TNBC) and high molecular–risk hormone receptor (HR)–positive breast cancer.

 Other key eligibility criteria included histologically confirmed invasive breast cancer; clinically or radiologically measurable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 25 mm; no prior exposure to cytotoxic regimens for this malignancy; no prior chemotherapy or prior radiation therapy to the ipsilateral breast for this malignancy; and an ECOG performance status of 0 or 1. Prior treatment with bis-phosphonate therapy was allowed.

The primary objective of the study is to determine whether adding experimental agents to standard neoadjuvant medications increases the probability of pCR over standard neoadjuvant chemotherapy for each biomarker signature established at trial entry.

In the current analysis, investigators assessed pCR and early EFS across different disease subtypes within the I-SPY 2 trial to enhance the understanding of patient outcomes and uncover potential signals of tumor responsiveness.

To build the rare breast tumor cohort, investigators reviewed pathology reports and histologic images of research biopsies from 2116 patients enrolled in the trial between 2010 and 2022. Histologic images of research biopsies, local biopsy, and surgical pathology reports were centrally reviewed, and tumors were accordingly classified as either rare or NST.

Most patients in both groups had HR-positive, HER2-negative disease (rare tumor group, 55.0%; NST group, 42.2%), followed by TNBC (36.6%; 35.2%) and HER2-positive disease (8.5%; 22.6%; 

 = .0002). The median age was 50.9 years in the rare tumor group and 48.3 in the NST group (

 = .008); mean weights were 74.8 kg and 75.8 kg, respectively (

 = .47). Most patients were White (rare tumor group, 85.5%; NST group, 78.8%; 

 = .16). Hispanic patients comprised 13.4% and 13.7% of patients in the rare tumor and NST groups, respectively (

“The rare breast tumor cohort had an overrepresentation of HR-positive, HER2-negative disease. HER2-positive disease was overrepresented in the NST cohort,” Thomas noted.

Receptor-based subtype distributions among these 2 groups were also assessed. As expected, there was an overrepresentation of TNBC among patients with metaplastic disease, Thomas noted.

There were a total of 6 response predator subtypes, which incorporate immune DNA repair deficiencies and luminal signatures with tumor HR and HER2-positive status. These included S1; S2; S3; HER2-Immune-DRD+ (S4); S5; S6; and unknown.

“Note, for example, S3, or the immune-positive signature, which suggests a vulnerability to immune therapy. [This] is overrepresented in metaplastic breast cancer and seen in several of the other breast cancer subtypes,” Thomas added.

EFS also differed among the groups, with the rare breast tumor group experiencing inferior EFS compared with the NST group (

= .021). Looking at individual tumor histology, patients with metaplastic and lobular breast cancer subtypes had a lower EFS vs those in the NST cohort in this early follow-up period (

Furthermore, pCR was found to correlate with EFS in both the NST (

 < .0001) and rare breast tumor cohorts (

 = .013). In the NST cohort, 668 patients experienced a pCR, and 28 patients achieved a pCR in the rare breast tumor cohort.

Disclosures: Dr Thomas disclosed the following relationships: stock and other ownership interests with Bristol-Myers Squibb, Doximity, Gilead Sciences, Johnson & Johnson, and Pfizer; serving in a consulting or advisory role for AstraZeneca; receiving institutional research funding from Merck and Sanofi; and having up-to-date royalties.

Thomas A, Wolf DM, Balassanian R, et al. Therapeutic response and outcomes with uncommon breast cancer subtypes in the I-SPY trial 2010-2022. 

 2024, 42(suppl 23):1. doi:10.1200/JCO.2024.42.23_suppl.1

I-SPY TRIAL: neoadjuvant and personalized adaptive novel agents to treat breast cancer (I-SPY). ClinicalTrials.gov. Updated April 23, 2024. Accessed August 9, 2024. https://clinicaltrials.gov/study/NCT01042379

High pCR rates were observed for patients with uncommon breast cancer subtypes who received response-predictive subtype–optimized therapy.

RPS-Optimized Checkpoint Inhibition Bolsters pCR in Patients With Select Rare Breast Cancers

EV plus pembrolizumab in mUC - bladder cancer: © Sebastian Kaulitzki - stock.adobe.com

The combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) improved survival outcomes vs platinum-based chemotherapy with no detriment to global health status (GHS)/quality of life (QOL), pain, or functioning in patients with previously untreated, locally advanced or metastatic urothelial cancer, according to findings from a study assessing patient-reported outcomes (PROs) from the phase 3 EV-302 trial (NCT04223856).

, showed that the median time to pain progression (TTPP) was 14.2 months (95% CI, 6.6-not reached [NR]) in the enfortumab vedotin plus pembrolizumab arm (n = 376) vs 10.0 months (95% CI, 5.9-NR) in the chemotherapy arm (n = 355; HR, 0.92; 95% CI, 0.72-1.2; 2-sided 

= .48). The median time to confirmed deterioration (TTCD) was 5.9 months in the enfortumab vedotin plus pembrolizumab arm vs 3.2 months in the chemotherapy arm (HR, 0.98; 95% CI, 0.79-1.2).

“PRO data presented here complement the published clinical efficacy and safety data, add the patient perspective, and support the use of enfortumab vedotin plus pembrolizumab for patients with locally advanced, metastatic urothelial cancer,” lead study author Eiji Kikuchi, PhD, of the St. Marianna University School of Medicine in Kawasaki City, Kanagawa, Japan, stated in the presentation.

Previously, EV-302 showed that patients who received enfortumab vedotin plus pembrolizumab achieved a median progression-free survival of 12.5 months (95% CI, 10.4-16.6) vs 6.3 months (95% CI, 6.2-6.5) with chemotherapy (HR, 0.45; 95% CI, 0.38-0.54; 

Furthermore, at a median follow-up of 17.2 months, the combination yielded a median overall survival of 31.5 months (95% CI, 25.4-NR) vs 16.1 months (95% CI, 13.9-18.3) with chemotherapy (HR, 0.47; 95% CI, 0.38-0.58; 

< .001). Investigators deemed the safety profile of enfortumab vedotin plus pembrolizumab to be generally manageable and consistent with previous studies of the agents.

approved enfortumab vedotin plus pembrolizumab

 in 2023 for the treatment of patients with locally advanced or metastatic urothelial cancer.

 The combination is now considered the frontline standard of care for this population.

Investigators collected PRO data from EV-302 at baseline, including on day 1, prior to patients’ first dose, and post-randomization; weekly for 12 weeks; and every 3 weeks beyond the end of treatment and progression through survival follow-up. Patients completed the EORTC Core Quality of Life questionnaire (EORTC-QLQ-C30), which has a score range of 0 to 100. A higher score represents greater symptom burden, higher functioning, and greater QOL. The EORTC-QLQ-C30 assesses cancer-related symptoms, such as constipation, appetite loss, dyspnea, diarrhea, insomnia, fatigue, pain, nausea, and vomiting; physical, cognitive, emotional, role, and social function outcomes; and QOL/GHS. Patients also completed the Brief Pain Inventory—Short Form (BPI-SF) questionnaire, which has a score range of 0 to 10, with a higher score representing more pain. The BPI-SF assessed pain categories including worst pain, average pain, least pain, pain right now, pain interference, and location of pain.

“One notable aspect of the present study is that it collected PRO data beyond the end of treatment and beyond stage progression,” Kikuchi emphasized.

Prespecified study end points that were included in the hierarchical statistical testing plan included TTPP and mean change from baseline in worst pain at week 26. Prespecified descriptive analyses included data on change from baseline and TTCD. Patients with moderate or severe pain at baseline (enfortumab vedotin plus pembrolizumab arm, n = 128; chemotherapy arm, n = 128) were prespecified as a subgroup of interest.

In the enfortumab vedotin plus pembrolizumab arm, patients’ mean worst pain level per BPI-SF was 3.1 (standard deviation [SD], 2.8). This level was 3.3 (SD, 3.0) in the chemotherapy arm.

Regarding EORTC-QLQ-C30 outcomes, patients in the enfortumab vedotin plus pembrolizumab arm had a mean GHS/QOL score of 62.4 (SD, 22.5). The mean cognitive, social, emotional, physical, and role functioning scale scores in this arm were 84.3 (SD, 19.6), 77.3 (SD, 27.4), 75.5 (SD, 20.7), 76.5 (SD, 22.7), and 75.8 (SD, 28.3), respectively. In the chemotherapy arm, patients had a mean GHS/QOL score of 60.3 (SD, 25.4). The mean cognitive, social, emotional, physical, and role functioning scale scores in this arm were 83.9 (SD, 19.9), 76.3 (SD, 26.3), 74.6 (SD, 22.0), 72.8 (SD, 24.3), and 73.2 (SD, 29.4), respectively.

Predefined clinically meaningful thresholds for change in worst pain per the BPI-SF were not met in either arm (mean least square [LS], –0.58; 95% CI, –1.05 to –0.11; 2-sided 

= .015). However, patients in the enfortumab vedotin plus pembrolizumab arm reported improved pain compared with baseline, and larger improvements in pain were observed in the enfortumab vedotin plus pembrolizumab arm vs the chemotherapy arm.

In both arms, patients with moderate or severe pain at baseline had clinically meaningful improvements in worst pain (mean LS, –0.5; 95% CI, –1.0 to –0.02; 

= .04). Greater improvements in pain were observed in the enfortumab vedotin plus pembrolizumab arm vs the chemotherapy arm in this subgroup.

Patients in the enfortumab vedotin plus pembrolizumab arm had a transient worsening in GHS/QOL score at week 3, and scores returned to baseline at week 4. Patients in the chemotherapy arm had a worsening of GHS/QOL score from week 1 through week 17, and scores retuned to baseline from week 20. The mean LS was 2.5 (95% CI, 0.4-4.7; 

Patients in the enfortumab vedotin plus pembrolizumab arm had improvements across all functioning domains compared with patients in the chemotherapy arm based on changes from baseline within the first 26 weeks. The respective mean LS for role, physical, social, cognitive, and emotional functioning between the enfortumab vedotin plus pembrolizumab and chemotherapy arms were 4.13 (95% CI, 1.47-6.79; 

= .0007), 2.57 (95% CI, –0.07 to 5.22; 

= .0040); and 1.89 (95% CI, –0.19 to 3.97; 

“Data collected across the entire patient journey was a notable approach and was associated with differences in compliance between the 2 arms,” Kikuchi concluded.

The study authors noted that findings from this study may inform the design of future trials.

Dr Kikuchi reports consulting or advisory roles with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb-Ono Pharmaceutical, Chugai Pharma, Janssen, Merck/Pfizer, and MSD; Speakers’ Bureau participation with Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb-Ono Pharmaceutical, Chugai Pharma, Ferring; Janssen, Kissei Pharmaceutical, Kyorin, Kyowa Kirin International, Merck, MSD, Nippon Kayaku, Nippon Shinyaku, Pfizer, Sanofi, Taiho Pharmaceutical, and Takeda; and research funding from Chugai Pharma (Inst), Kissei Pharmaceutical (Inst), Kyorin (Inst), Kyowa Kirin International (Inst), Nihonkayaku (Inst), Nippon Shinyaku (Inst), Otsuka (Inst), Sanofi (Inst), Taiho Pharmaceutical (Inst), and Takeda (Inst).

Kikuchi E, Loriot Y, Van der Heijden M, et al. Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC). 

. 2024;42(suppl 23):108. doi:10.1200/JCO.2024.42.23_suppl.108

Powles T, Valderrama BP, Gupta S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. 

. 2024;390(10):875-888. doi:10.1056/NEJMoa2312117

FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. FDA. December 15, 2023. Accessed August 9, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-enfortumab-vedotin-ejfv-pembrolizumab-locally-advanced-or-metastatic-urothelial-cancer

Enfortumab vedotin plus pembrolizumab improved survival vs chemotherapy with no QOL detriment in previously untreated metastatic urothelial cancer.

Enfortumab Vedotin/Pembrolizumab Does Not Negatively Impact QOL in Metastatic Urothelial Cancer

The addition of carbon-ion radiotherapy (CIRT) to the combination of durvalumab (Imfinzi) plus tremelimumab (Imjudo; the STRIDE regimen) demonstrated safety in the treatment of patients with advanced hepatocellular carcinoma (HCC) and macrovascular invasion, according to data from the phase 1b DEPARTURE trial (jRCT2031210046).

 showed that patients treated with the regimen in cohort A (n = 3) and cohort B (n = 12) did not experience any dose-limiting toxicities (DLTs). All patients (n = 15) experienced any-grade treatment-emergent adverse effects (TEAEs), and treatment-related TEAEs were reported in 93.3% of patients. The rates of grade 3, grade 4, and grade 5 TEAEs were 46.7%, 13.3%, and 6.7%, respectively. The respective rates of grade 3, grade 4, and grade 5 treatment-related TEAEs were 26.7%, 6.7%, and 0%.

Serious TEAEs occurred in 33.3% of patients, although none were observed in cohort A. The rate of serious treatment-related AEs was 26.7%.

“The safety of durvalumab plus tremelimumab in combination with particle therapy has been confirmed in advanced HCC with macrovascular invasion,” lead study author Keisuke Koroki, MD, PhD, of the Department of Gastroenterology in the Graduate School of Medicine at Chiba University in Japan, said in a presentation of the data.

 for the treatment of patients with unresectable HCC based on data from the phase 3 HIMALAYA trial (NCT03298451).

Koroki explained that radiotherapy is associated with the release of cancer antigens and antigen presentation. Accordingly, a synergistic effect is anticipated when radiotherapy is combined with immune checkpoint inhibitors.

DEPARTURE was a multicenter, open-label, single-arm trial that enrolled patients at least 20 years of age with histologically confirmed HCC and a diagnosis of macrovascular invasion. Patients must have been ineligible for locoregional therapy for unresectable HCC, and a history of at least 1 prior systemic therapy regimen was required for those enrolled onto cohorts A and B. Other inclusion criteria consisted of an ECOG performance status (PS) of 0 or 1, and a Child-Pugh A score.

Enrolled patients in cohort A received 1500 mg of durvalumab alone on day 1, and those in cohort B were given the STRIDE regimen consisting of 1500 mg of durvalumab plus 300 mg of tremelimumab. On day 8, all patients received CIRT for 4 consecutive days. All patients then received 1500 mg of durvalumab once every 4 weeks until disease progression.

Safety, including the incidence of DLTs, served as the trial’s primary end point. Secondary end points included overall survival (OS), 6-month OS rate, objective response rate, 6-month progression-free survival (PFS) rate, and time to progression.

DLTs were defined as the following: grade 4 or higher neutropenia; grade 4 or higher anemia; grade 3 or higher thrombocytopenia with bleeding; grade 4 or higher non-immunological AEs; grade 4 or higher AEs excluding endocrine disorders; grade 3 or higher non-immunological AEs that do not improve within 30 days of onset despite appropriate therapy; and grade 3 or higher immunological AEs that do not improve within 30 days despite appropriate therapy, with some exceptions.

All 15 patients enrolled in cohorts A and B were from Japan. The median age was 69.0 years (range, 25.0-81.0), and the median body weight was 63.1 kg (range, 53.2-88.2). The majority of patients were male (86.7%) and had an ECOG PS of 0 (86.7%). All patients had Barcelona Clinic Liver Cancer stage C disease, and 13.3% of patients were heavy drinkers. Patients had a Child-Pugh score of 5 (66.7%) or 6 (33.3%). The median alpha-fetoprotein was 213.7 ng/kg (range, 3.5-270208.0).

Histologies included HBV surface antigen–positive HCC (20.0%), anti-HCV–positive disease (13.3%), and other (66.7%). The majority of patients (66.7%) had at least 8 tumors, and the median maximum tumor size was 91.1 mm (range, 32-221.8). Portal vein invasion included Vp0 (6.7%), Vp2 (46.7%), Vp3 (20.0%), and Vp4 (26.7%); hepatic vein invasion consisted of Vv0 (86.7%), Vv2 (6.7%), and Vv3 (6.7%). No patients had intrahepatic bile duct invasion. Notably, 26.7% of patients were naive to systemic therapy.

Efficacy data showed that no patients in either cohort experienced responses. Stable disease was reported in 11 patients. Ten patients had progressive disease, 7 of whom had experienced stable disease. Treatment was ongoing for 2 patients in cohort B. One patient withdrew, and 2 patients discontinued treatment due to AEs, including 1 patient who died.

The median PFS was 4.67 months (95% CI, 1.35-6.44) for the overall population, 4.67 months (95% CI, 4.63-4.67) for cohort A, and 3.84 months (95% CI, 1.12-6.64) for cohort B. The median OS was 10.40 months (95% CI, 5.62-15.16) for the overall population, 28.22 months (95% CI, 5.54-50.89) for cohort A, and 10.20 months (95% CI, 4.31-16.09) for cohort B.

Additional safety data showed the most common any-grade TEAEs reported in at least 10% of the overall population included pyrexia (60.0%), rash (33.3%), increased lipase (33.3%), radiation skin injury (33.3%), decreased appetite (26.7%), constipation (20.0%), diarrhea (20.0%), malaise (20.0%), increased alanine aminotransferase (20.0%), increased amylase (20.0%), increased aspartate aminotransferase (20.0%), COVID-19 (13.3%), interstitial lung disease (13.3%), pleural effusion (13.3%), abdominal pain (13.3%), and decreased platelet count (13.3%).

“The [STRIDE plus CIRT] combination, especially the irradiation of tumors with macrovascular invasion using CIRT, hold promise in managing prognostic determinant tumors and potentially enhancing OS,” Koroki concluded.

Disclosures: Dr Koroki did not disclose any relationships.

Koroki K, Ogasawara S, Makishima H, et al. Phase Ib trial of durvalumab plus tremelimumab in combination with particle therapy in patients with advanced hepatocellular carcinoma with macrovascular invasion: DEPARTURE trial. 

. 2024;42(suppl 23):34. doi:10.1200/JCO.2024.42.23_suppl.34

FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma. FDA. October 21, 2022. Accessed August 8, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-unresectable-hepatocellular-carcinoma

CIRT plus durvalumab and tremelimumab was safe in patients with advanced hepatocellular carcinoma with macrovascular invasion.



CIRT Plus Durvalumab/Tremelimumab Is Safe in Advanced HCC With Macrovascular Invasion

Treatment with the second-generation KRAS G12C inhibitor olomorasib plus pembrolizumab (Keytruda) produced favorable safety in 

G12C–mutant non–small cell lung cancer (NSCLC), supporting the continued development of this combination in the first-line setting, according to data from the phase 1/2 LOXO-RAS-20001 trial (NCT04956640) presented during the

In efficacy evaluable patients with metastatic disease being treated in the first line (n = 17), the objective response rate (ORR) with the combination was 77% and was composed entirely of partial responses (PR). The best responses to treatment included stable disease (SD; 12%) and progressive disease  (PD; 6%), although 6% of patients were not evaluable (NE). At a median follow-up of 5.5 months, the median progression-free survival (PFS) was NE (95% CI, 3.6-NE). The estimated 6- and 12-month PFS rates were both 72.8%.

 G12C–mutant NSCLC (n = 43), the ORR was 40%, and included all PRs. PD and SD were the best responses in 42% and 16% of patients, respectively; best response was NE in 2% of patients. Notably, 81% of previously treated patients had received prior immunotherapy.

Across both groups, the median time on treatment was 3.5 months (range, 0-17), the median time to response was 1.4 months, the median duration of response was NE.

“Olomorasib in combination with pembrolizumab demonstrates promising antitumor activity,” lead study author Yutaka Fujiwara, MD, PhD chief of the Department of Thoracic Oncology at Aichi Cancer Center Hospital in Aichi, Japan, stated in an oral presentation of the data. “We have responses at both the 50 mg and 100 mg dose level regardless of PD-L1 score and previous treatment, including immunotherapy and KRAS G12C inhibitor.”

Immunotherapy remains the cornerstone of first-line treatment for patients with 

G12C–mutant NSCLC; however, outcomes for these patients remain suboptimal.

 G12C-mutant NSCLC remains poor, despite the approval of first-generation KRAS inhibitors, which are currently limited to second or later line use. Further progress may be achieved with the addition of targeted therapy to immunotherapy in NSCLC,” Fujiwara added.

Olomorasib, a potent and selective second-generation inhibitor of GDP-bound KRAS G12C, is emerging as a candidate to address these unmet needs. Previously reported data from the LOXO-RAS-20001 study showed that olomorasib monotherapy demonstrated a favorable safety profile, with treatment-related adverse events (TRAEs) being predominantly grade 1. Notably, this safety profile was consistent even in patients who had discontinued previous KRAS G12C inhibitors due to toxicity, indicating a manageable toxicity profile.

Moreover, efficacy for olomorasib monotherapy was consistent across a range of 

G12C-mutant solid tumors. Among patients with NSCLC who were previously treated with a KRAS G12C inhibitor (n = 39), the agent produced an ORR of 41%, with 63% having received a KRAS G12C inhibitor as their immediate prior therapy. The median PFS was 8.1 months (95% CI: 5.6-15.6). Notably, preliminary CNS activity was seen, with CNS responses observed in patients with NSCLC and measurable brain metastases.

LOXO-RAS-20001 is an open-label, multicenter, study evaluating the safety, tolerability and preliminary efficacy of olomorasib in patients with advanced solid tumors harboring 

mutations. The study begins with a phase 1a dose escalation phase evaluating olomorasib monotherapy in

G12C-mutant solid tumors, as well as a phase 1b dose expansion and optimization phase assessing olomorasib as both monotherapy and in combination with other agents. The dose expansion phase is further divided into the following 5 parts: NSCLC (part B), CRC (part C), other solid tumors (part D), NSCLC with prior KRAS G12C inhibitor exposure (part E) and first-line NSCLC (part G).

Patients at least 18 years of age with locally advanced or metastatic solid tumors harboring a 

G12C mutation were enrolled onto the study. Other eligibility criteria included measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and no prior exposure to a KRAS G12C inhibitor except where indicated. In part B4, patients were permitted to have prior exposure to chemotherapy, anti–PD-L1 therapy, or a KRAS G12C inhibitor. No prior therapy for metastatic disease was permitted in part G.

The study’s primary objectives were to establish safety and tolerability, as well as the maximum tolerated dose and recommended phase 2 dose of the agent. Key secondary end points included pharmacokinetics; and ORR and duration of response per RECIST 1.1 criteria.

The current analysis features patients with 

G12C-mutant NSCLC who were enrolled onto part B4 (n = 48) and part G (n = 16) of the study and received pembrolizumab plus olomorasib.

 The data cutoff was March 18, 2024. Patients in this population were treated with pembrolizumab plus oral olomorasib at a twice-daily dose of 50 mg (n = 15) or 100 mg (n = 49).

The median age was 67 years of age (range, 42-83), and the majority of patients were male (53%), White (47%), and had an ECOG PS of 1 (75%). Brain metastases were observed in 38% of patients and 31% had first-line metastatic disease. Regarding PD-L1 expression score, 28%, 27%, 27%, and 19% had a score of 50% or greater, less than 1%, between 1% to 49%, and unknown, respectively.

“When we look at the PD-L1 scores, there was a well-balanced distribution,” Fujiwara added.

The median number of prior systemic lines of therapy was 2 (range, 0-8), and 69% of patients received either platinum-based chemotherapy plus a PD-L1 inhibitor (82%); platinum-based chemotherapy alone (18%); or a KRAS G12C inhibitor (39%). Among patients who were previously exposed to a KRAS G12C inhibitor, patients discontinued treatment due to disease progression (76%), toxicity (18%), and other reasons (6%).

Regarding safety, any-grade treatment-related adverse effects (TRAEs) were observed in 70% of patients across all dose levels and populations; 86% experienced any grade treatment-emergent effects (TEAEs). TRAEs required dose holds in 25% of patients and olomorasib dose reductions in 17% of patients in the overall population. Only 3% and 11% of patients permanently discontinued olomorasib vs pembrolizumab, respectively, due to TRAEs; 5% discontinued both drugs due to TRAEs.

Common TRAEs in 10% or more of patients included diarrhea (any grade, 23%; grade 3, 13%), fatigue (16%, 0%), alanine transaminase (ALT) increase (20%; 6%), pruritis (19%; 3%), aspartate transaminase (AST) increase (16%; 8%), and nausea (14%; 0%).

The incidence of TEAEs in at least 10% of patients included diarrhea (any-grade, 28%; grade 3 or higher, 13%), fatigue (27%; 0%), ALT increase (25%; 8%), pruritis (25%; 3%), nausea (23%; 0%), arthralgia (19%; 0%), AST increase (17%; 8%), vomiting (17%; 0%), anemia (16%; 2%), decreased appetite (14%; 2%), cough (13%; 0%), dyspnea (11%; 5%), hypokalemia (11%; 3%), and headache (11%; 0%).

Investigators noted that grade 2 or higher diarrhea was unusually brief, with a median duration of 9 days. These events resolved to grade 1 or baseline with dose modification and antidiarrheals in 92% of patients. All grade 3 ALT/AST resolved to grade 1 or baseline after a median of 6 days following dose modification and/or corticosteroids. No grade 2 or higher ALT/AST elevation had high-risk features. Elevated liver function tests were also less than 10x ULN without total bilirubin elevation and otherwise asymptomatic.

“Given these promising results, we are currently conducting a global, registrational, phase 3 trial called SUNRAY-01 [NCT06119581]”, Fujiwara concluded. The study will compare first-line olomorasib plus pembrolizumab with pembrolizumab plus placebo in 

G12C-mutant, locally advanced or metastatic NSCLC with a PD-L1 expression of at least 50%; or first-line olomorasib vs placebo in combination with pembrolizumab, pemetrexed and platinum-based chemotherapy in patients with this tumor type regardless of PD-L1 expression. The trial is currently open to enrollment.

Disclosures: Dr Fujiwara disclosed honoraria from Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb Japan, Chugai Pharma, Daiichi Sankyo/UCB Japan, Lilly Japan, Merck, MSD, Nihonkayaku, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda, Yakult Pharmaceuticals; serving in a consulting or advisory role for AstraZeneca, Chiome Bioscience, Daiichi Sankyo, MSD, Ono Pharmaceutical, Otsuka; and institutional research funding from Abbvie, Amgen, Anheart Therapeutics, AstraZeneca, Bristol-Myers Squibb Japan, Chugai Pharma, Incyte, Lilly Japan, Merck Serono, MSD (Inst)

Fujiwara Y, Burns TF, Dragnev KH, et al. Efficacy and safety of olomorasib (LY3537982), a second-generation KRAS G12C inhibitor (G12Ci), in combination with pembrolizumab in patients with KRAS G12C-mutant advanced NSCLC. 

 2024, 42(suppl 23):195.doi:10.1200/JCO.2024.42.23_suppl.195

Updated data from the phase 1/2 study of olomorasib in KRAS G12C-mutant advanced solid tumors presented at the 2024 ASCO® Annual Meeting. News release. Lilly. June 1, 2024. Accessed August 8, 2024. https://investor.lilly.com/news-releases/news-release-details/updated-data-phase-12-study-olomorasib-kras-g12c-mutant-advanced

Study of LY3537982 in cancer patients with a specific genetic mutation (KRAS G12C). Clinicaltrials.gov. Updated July 29, 2024. Accessed August 8, 2024. https://clinicaltrials.gov/study/NCT04956640

Olomorasib plus pembrolizumab demonstrated responses in first-line metastatic KRAS G12C–mutant non–small cell lung cancer.

Olomorasib Plus Pembrolizumab Generates Antitumor Activity in KRAS G12C+ NSCLC

Treatment with pacritinib (Vonjo) at 200 mg given twice daily was found to be tolerable with a reasonable safety profile in patients with solid tumors harboring 1q21.3 copy number amplifications, according to data from a phase 1b/2 trial (NCT04520269) presented at the 

Regarding treatment toxicity, 2 dose-limiting toxicities (DLTs) of grade 3 transaminitis were recorded at dose level 1 of 200 mg twice per day; 2 patients treated at this dose level also experienced intolerable grade 2 rashes, although these toxicities were resolved with antihistamines. No DLT were reported when pacritinib was dosed at 200 mg in the morning and 100 mg at night (dose level 2). When pacritinib was re-escalated to 200 mg twice per day (dose level 3), no additional DLTs occurred.

The adverse effect (AE) profile of the agent was similar to the known toxicity profile of pacritinib. Overall, 5 patients experienced grade 3 transaminitis; notably, all of these patients had known liver metastases, and 4 were found to have worsening liver disease progression. All toxicities resolved without sequelae after pacritinib was discontinued.

Regarding efficacy, no patients (n = 24) with solid tumors harboring 1q21.3 copy number alterations experienced responses. Two patients had stable disease. One patient with pancreatic cancer had a progression-free survival (PFS) of 24.9 weeks, and 1 patient with cholangiocarcinoma had a PFS of 15.9 weeks.

“While no objective responses were observed thus far, meaningful disease control was observed in 2 patients with pretreated hepatobiliary tumors,” Joline Lim, MD, of the National University Cancer Institute, in Singapore, said during a presentation of the data.

Copy number alterations of 1q21.3 are more frequently observed in recurrent and metastatic diseases vs primary tumors or healthy individuals, and detection of this copy number alteration and immunohistochemistry testing has revealed a correlation between 1q21.3 copy number alterations and IRAK1 overexpression. The JAK2 inhibitor pacritinib, which is 

approved by the FDA for treating select patients with intermediate- or high-risk primary or secondary myelofibrosis

The phase 1b/2 study assessed the safety and effectiveness of pacritinib in patients with refractory solid tumors using plasma 1q21.3 copy number alterations as a biomarker for selection.

The study used a 3+3 dose-escalation design, initially followed by dose expansion in 2 cohorts: 1 for patients with breast cancer and another for those with other solid tumors. Due to patient enrollment challenges, the investigation was modified to a single dose-expansion cohort. Serial tumor and plasma samples were also collected for translational studies to explore the mechanistic impact of IRAK1 inhibition on the tumor microenvironment and its effects on immune function and biomarker modulation.

Investigators pre-screened 555 patients for 1q21.3 copy number alterations, of which 461 patients passed quality control with readout. A total of 28.6% of these patients (n = 132) tested postitive for 1q21.3 copy number alterations. Of patients who tested positive, they presented with the following tumor types: colorectal (35.7% of screened patients positive for 1q21.3 copy number alterations), breast (36.6%), hepatobiliary (20.0%), lung (34.6%), gynecological (22.0%), genitourinary (19.4%), upper gastrointestinal (9.1%), musculoskeletal (22.2%), head and neck (40.0%), and other (18.2%).

At dose level 1, 6 patients were treated with 200 mg twice daily; at dose level 2, 3 patients received pacritinib at 200 mg once in the morning and 100mg once at night; at dose level 3, 3 patients received pacritinib at 200 mg twice daily; and in the expansion cohort, 12 patients were treated with pacritinib at 200 mg twice daily, where 2 patients were ongoing treatment.

In the 24 patients enrolled on the study, the median age was 60 years (range, 25-78), and the median 1q21.3 copy number alterations was 1.28 (range, 1.14-2.50). Patients received a median of 5 prior lines of treatment in metastatic setting (range, 2-11), including 25% of patients who underwent prior immunotherapy. Moreover, patients presented with colorectal (37.5%), breast (8.3%), hepatobiliary (33.3%), lung (8.3%), other (8.3%), or gynecological (4.2%) tumors.

Notably, 3 patients with paired tumor biopsies at baseline and 2 weeks after starting pacritinib treatment did not experience statistically significant changes in the percentage of various immune cell subpopulations. In these patients, there was a trend toward an increase in CD8-positive cytotoxic T cells (2.77% vs 8.57%; 

 = .07) and a potential increase in the population of PD-L1–positive cells (0.77% vs 3.00%; 

"Further translational studies to understand the effects of pacritinib using serial tumor and plasma samples are underway," Lim concluded.

Disclosures: Dr Lim reported speaking, consultancy, and advisory relationships with AstraZeneca, DKSH, Eisai, Gilead, MSD, Novartis, Pfizer, Pierre-Fabre, and Roche; and research relationships with Sobi Inc, Dalichi Sankyo, Taiho pharmaceuticals, Synthon pharmaceuticals.

Lim JSJ, Yee AM, Yeong J, et al. phase lb/ll study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients with solid tumors harboring the 1q21.3 copy number amplification. 

. 2024;42(suppl 23):43. doi:10.1200/JCO.2024.42.23_suppl.43

Pacritinib was tolerable with a reasonable safety profile in patients with solid tumors harboring 1q21.3 copy number amplifications.

Pacritinib Demonstrates Safety in Solid Tumors Harboring 1q21.3 Amplifications

Patients from East Asia with treatment-naive 

 fusion-positive non–small cell lung cancer (NSCLC) who received the RET inhibitor selpercatinib (Retevmo) experienced a progression-free survival (PFS) benefit compared with those who were treated with chemotherapy with or without pembrolizumab (Keytruda), according to findings from the phase 3 LIBRETTO-431 trial (NCT04194944) presented during the 

. Investigators noted that the results were consistent with previously presented data from the overall population of LIBRETTO-431 and support the use of selpercatinib as first-line treatment.

At a median follow-up of 19.4 months in the selpercatinib arm (n = 75) and 21.2 months in the control arm (n = 41), the median PFS was not yet reached (95% CI, 16.4-not evaluable) vs 11.1 months (95% CI, 7.0-16.8), respectively. The 12-month PFS rates were 72.8% vs 41.7%, respectively. Additionally, the overall response rate (ORR) was 86.7% (95% CI, 76.8%-93.4%) in the selpercatinib arm compared with 61% (95% CI, 44.5-75.8) in the chemotherapy arm.

“We cannot always assume that effective therapies in a general population will still be effective and safe in subpopulations,” David R. Spigel, MD, chief scientific officer at Sarah Cannon Research Institute in Nashville, Tennessee, said in a news release.

 “These outstanding results provide confidence that selpercatinib is an effective and safe treatment for East Asian patients with newly-diagnosed 

FDA granted regular approval to selpercatinib

 in September 2022 for the treatment of adult patients with locally advanced or metastatic NSCLC harboring a 

 gene fusion, as detected by an FDA-approved test. The regulatory decision was supported by findings from the phase 1/2 LIBRETTO-001 trial (NCT03157128).

LIBRETTO-431 was an open-label study that enrolled adult patients with pathologically confirmed unresectable stage IIIB, IIIC, or IV nonsquamous NSCLC who had not received prior systemic treatment for metastatic disease. Eligible patients had measurable disease per RECIST 1.1 criteria, an ECOG performance status of 2 or less, and adequate organ function; those with brain metastases were included if they were asymptomatic or had been neurologically stable for at least 2 weeks prior to random assignment. Patients with additional oncogenic drivers in NSCLC, those who received prior systemic therapy for advanced disease, and those with active cardiovascular disease, active uncontrolled infections requiring treatment, or uncontrolled disease-related pericardial effusion or pleural effusion were not included in the trial.

Patients were initially randomly assigned 1:1 to receive 160 mg of selpercatinib twice daily via continuous 21-day cycles or 500 mg/m

 of pemetrexed with vitamin supplementation along with the investigator’s choice of platinum therapy or cisplatinwith or without 200 mg of pembrolizumab administered every 21 days. After a protocol amendment, patients were randomly assigned 2:1 to the investigational or control arm, for a final ratio of random assignment of 1.6:1. Stratification occurred based on geographic region (East Asia vs elsewhere), brain metastases at baseline (absent or unknown vs present), and whether the investigator had intended to treat the patient with or without pembrolizumab prior to random assignment.

The primary end point was PFS by blinded independent central review. Secondary end points included overall survival, investigator-assessed PFS, ORR, and duration of response.

In terms of safety, the most common any-grade adverse effects (AEs) in the selpercatinib arm (n = 91) included elevated aspartate aminotransferase levels (AST; 73.6%), increased alanine transaminase levels (ALT; 70.3%), hypertension (60.4%), increased blood bilirubin (52.7%) and diarrhea (44.0%). In the control arm (n = 49), the most common any-grade AEs included anemia (61.2%), elevated AST levels (49.0%), leukopenia (49.0%), neutropenia (44.9%) and increased ALT levels (42.9%).

The median time on treatment in the selpercatinib arm was 16.6 months (SD ± 7.8) compared with 9.7 months (SD ± 7.9) in the control arm. Patients in both arms experienced at least 1 dose adjustment (86.8% vs 65.3%), AEs of grade 3 or higher severity (76.9% vs 51.0%), and AEs leading to treatment discontinuation (12.1% vs 2.0%), respectively. Two patients in the investigational arm experienced a fatal AE either on treatment or within 30 days of receiving the last dose.

Cheng Y, Loong HH, Zhou C, et al. Efficacy and safety of 1L selpercatinib in 

 fusion-positive NSCLC: LIBRETTO-431 East Asian subgroup analysis. 

. 2024;42(suppl 23):214. doi:10.1200/JCO.2024.42.23_suppl.214

East Asian patients with RET fusion-positive NSCLC experienced a PFS benefit when treated with selpercatinib vs chemotherapy with/without pembrolizumab.

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