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Association between empirical dietary inflammatory pattern (EDIP) and survival in patients with stage III colon cancer: Findings from CALGB/SWOG 80702 (Alliance).
Char, Sara K., Kumthekar, Priya , Guthrie, Katherine A. , Couture, Félix , Kuebler, J. Phillip, Kumar, Pankaj , Tan, Benjamin , Krishnamurthi, Smitha , Wolpin, Brian M. , Geoffroy, Francois J., Shields, Anthony F. , Ng, Kimmie , Char, Sara K., Shi, Qian , Zemla, Tyler , Ma, Chao , Cheng, En , Tabung, Fred K. , O’Reilly, Eileen M. , Meyerhardt, Jeffrey A. , Yuan, Chen

Journal of Clinical Oncology | June 4, 2025 | Volume: 43 | Issue: 17_suppl | Pages: No page available

10.1200/jco.2025.43.17_suppl.lba3509 Get It

LBA3509 Background: Systemic inflammation has been implicated in colon cancer progression. We examined whether intake of a proinflammatory diet is associated with survival among patients (pts) with stage III colon cancer. Methods: This prospective cohort study was nested within a randomized phase III trial of adjuvant therapy in pts with stage III colon cancer who had undergone curative-intent resection. EDIP score – a validated tool to classify the inflammatory nature of diets – was derived as a cumulative exposure using data from food-frequency questionnaires completed within 6 weeks of randomization and 14-16 months (mo) after randomization. Cox proportional hazards regression was used to assess the associations of EDIP with disease-free survival (DFS) and overall survival (OS). Results: Of 1625 included pts, the mean (SD) age was 60.9 (10.5) years (yrs). Compared to pts in the lowest EDIP quintile, pts in the highest quintile (a more inflammatory diet) were younger (58.7 ± 10.8 vs 61.3 ± 9.5 yrs old) and more likely to be female (64.0% vs 48.9%) and have worse performance status (ECOG 1-2: 35.7% vs 19.4%). Pts in the highest quintile were less likely to be White (76.6% vs 92.0 %) and more likely to be Black (15.4% vs 3.7%). Baseline aspirin use, assigned chemotherapy (3 mo vs 6 mo), and assigned pharmacotherapy (celecoxib vs placebo) were not significantly different across EDIP quintiles. Compared with pts in the lowest EDIP quintile, pts in the highest quintile had significantly worse OS (multivariable hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26-2.77, P trend =0.01), but not DFS (HR 1.36, 95% CI 0.99-1.86, P trend =0.22). Diet and physical activity jointly influenced OS. Those with lower EDIP scores (quintiles 1-4, 80% of the study population) and higher physical activity (≥9 MET-h/wk) had the best OS (HR 0.37, 95% CI 0.25-0.53) compared with pts in the highest EDIP quintile (20% of the study population) and lower physical activity (<9 MET-h/wk) ( P interaction <0.001). The association between higher EDIP and OS was consistent when analyzed by celecoxib and placebo treatment arms ( P interaction 0.54). The relationship between EDIP and OS did not differ significantly according to aspirin use, with HR 1.60 (95% CI 0.71-3.60) among aspirin users and HR 2.01 (95% CI 1.27-3.16) among aspirin non-users ( P interaction 0.06). Conclusions: Our findings suggest that greater intake of a proinflammatory dietary pattern is associated with worse OS in pts with stage III colon cancer. Regular physical activity may attenuate the association, and further investigation of diet and physical activity intervention is warranted. Support: U10CA180821, U10CA180882, U24CA196171, U10CA180863, CCS 707213, UG1CA233234, U10CA180820, U10CA180868, U10CA180888; https://acknowledgments.alliancefound.org. Pfizer; ClinicalTrials.gov Identifier: NCT01150045.
Removal of painful pelvic screws following spine fusion surgery: outcomes and complications
Mikula, Anthony L. , Pennington, Zach , Lakomkin, Nikita , Freedman, Brett A. , Sebastian, Arjun S. , Cross, William W., Elder, Benjamin D. , Fogelson, Jeremy L. , Pennington, Zach , Martini, Michael L. , Hamouda, Abdelrahman M. , Nassr, Ahmad , Ames, Christopher Pearson

Neurosurgical Focus | June 1, 2025 | Volume: 58 | Issue: 6 | Pages: E15

10.3171/2025.3.focus2510 | PMID 40450885 Get It

OBJECTIVE The purpose of this study was to evaluate the risks and benefits of removing painful pelvic/iliac screws in spine fusion surgery patients. METHODS A retrospective review identified patients who had traditional iliac and S2-alar-iliac (S2AI) screws removed for pain. The minimum follow-up was 24 months. RESULTS Fifty-two patients (75% women) were included with a mean age of 63 years, BMI of 28, and follow-up of 65 months. Most of the removed screws were S2AI (83%) compared with traditional iliac screws (17%). Forty-three patients (83%) had improvement in their pelvic screw related–pain following removal. Eight patients (15%) experienced lumbosacral mechanical complications following pelvic screw removal including sacral fracture (n = 3, 6%) and/or L4–5 or L5–S1 rod fracture (n = 7, 13%). On multivariable analysis, risk factors for mechanical complications following pelvic screw removal included a longer fusion construct (OR 1.34, p = 0.035), greater postoperative L4–S1 lordosis (OR 1.14, p = 0.04, ideal cutoff > 40°), and lack of bone morphogenetic protein (BMP; OR 0.03, p = 0.02). Ten patients (19%) underwent subsequent SI joint fusion following pelvic screw removal, and higher standing pelvic incidence (OR 1.10, p = 0.03) was the only independent predictor of SI fusion. CONCLUSIONS Removal of painful pelvic screws resulted in a high rate of postoperative pain relief, albeit with a risk of lumbosacral mechanical complications and subsequent SI joint fusion. Patients at risk for lumbosacral mechanical complications following pelvic screw removal included those with longer fusion constructs, more lordosis from L4 to S1 (> 40°), and lack of BMP. Patients at risk for receiving an instrumented SI joint fusion following pelvic screw removal included those with a higher pelvic incidence.
Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study
Babiker, Hani M. , Picozzi, Vincent J. , Chandana, Sreenivasa R , Melichar, Bohuslav, Kasi, Anup , Gang, Jin, Gállego, Javier , Bullock, Andrea J. , Chunyi, Hao, Hitre, Erika, Osipov, Arsen , Alés, Inmaculada, Dragovich, Tomislav, Lee, Woo Jin , Feeney, Kynan, Ueno, Makoto , Seufferlein, Thomas , Investigators, on behalf of the PANOVA-3 Study, Osipov, Arsen, Matrana, Marc , Blondin, Nicholas, Shroff, Rachna T. , Orr, Douglas, Anderson, Michael J. , Shields, Anthony F. , Hamm, John , Bullock, Andrea, Nagireddy, Sumana, Kolodney, Joanna, Dragovich, Tomislav, Maniam, Ajit, Sears, Judith D., Stilwill, Joseph, Cusnir, Mike , Niewiaroska, Anna, Small, William, Kasi, Anup, Tache, Jason, Ross, Sharona, Shihabi, Samer, Gandhi, Sunil, Reeves, J. N. , Green, Garrett , Feinstein, Trevor, Huyck, Timothy K., Ramdin, Nadia, Marsh, Robert , Jiang, Yixing , Hatoum, Hassan , Manda, Sudhir, Kochenderfer, Mark D., Illum, Henrik, Richards, Donald , Valilis, P., Wong, Lucas, Newton, Herbert B. , Abdelrahim, Maen, Einspahr, David, Siegel, Richard, McKenney, Scott, Narang, Mohit , Cárdenes, Higinia R. , Thanikachalam, Kannan , Raff, Joshua P. , Ye, Joseph , Behl, Deepti , Kam, Audrey E., DeRose, Paul, Tasneem, A. , Brenner, Warren, Santos, Jennifer De Los , Rausch, D C, Trikha, Gaurav, Gabrail, Nashat , Mowat, Rex B., Jahangir, Khawaja, Schumaker, Robert P. , Soffen, Edward , Bravin, Eric, Gupta, Mukul Kumar , Bedoya-Apraez, Ivan Dario, Kang, Tyler Y., Lemay, Frédéric , Vincent, Mark , Létourneau, Richard, Doehring, Christine, Haberkorn, Mike, Rußwurm, Karen, Chater, Jack, Küng, Marc , Schacher, Sabine, Passhak, Maria , Geva, Ravit , Hubert, Ayala, Golan, Talia , Senellart, Hélène, Trouilloud, Isabelle , Blan, Jean-Frederic, Dourthe, Luis-Marie, Roy, Florence Le, Martin-Babau, J., Greil, Richard , Schreil, Georg, Gerger, Armin , Eisterer, Wolfgang , Mercadé, T. Macarulla, Cubillo, Antonio , Pons, Francesc Valladares, Díaz, Inmaculada Alés, Rivera, Fernando , Sarvise, Mariano Ponz, Airoldi, Mario , Bellotti, Giovanna, Corsi, Domenico , Antonuzzo, Lorenzo , Melichar, Bohuslav, Holečková, Petra , Kotasek, Rostislav, Němeček, Radim , Cutsem, Eric van, Laethem, Jean‐Luc Van , Sym, Sun Jin , Kim, Jin Young , Oh, Sang Cheul , Park, Joon Oh, Kim, Jin Won , Lee, Myung Ah , Choi, Hye Jin, Kang, Seok Yun , Mruk, Andrzej, Freier, Beata, Kosakowska, Ewa Anna, Kocsis, Judit, Csőszi, Tibor , Hitre, Erika, Al-Farhat, Yousuf, Cang, Shundong , Jin, Gang , Zuo, Changzeng, Song, Lijie, Wu, Zheng , Gao, Jie , Zhang, Tao� , Wang, Yusheng , Yuan, Xin , Li, Zhi-Hua , Chen, Rufu , Cai, Xiujun , Zhu, Zhizhen, Bai, Yuxian , Bai, Chunmei, Yau, Thomas, Joubert, Warren , Wong, Ka Yeung Mark, Harris, Marion , Mišir, Ana, Faccio, Adilson , Cruz, Felipe Melo , Azevedo, Srergio De, Victorino, Ana Paula , Paiva, Tadeu Ferreira, Franke, Fábio , Tiscoski, Katsuki Arima , Parolla, Gabriel, Lilno, Flora, Siqueira, Mariana Bruno , Lyra, Marcos, Lira, Jose Luis Martinez, Oliva, Dolores Mendoza, Vazquez, Arturo, Luviano, Jesus Elvis Cabrera, Gutiérrez, Erika Castillo , Camargo, Vanessa Rosas, Guerra, Cristian Chavez, Flores, Osvaldo Hernandez, Contreras, Jessica Reyes, Villanueva, Ángel Gómez, Villanueva, Omar Zayas, Bullock, Andrea , Wyrwicz, Lucjan , Osipov, Arsen , De La Fouchardiere, Christelle , Lee, Woojin , Ueno, Makoto , Van Cutsem, Eric , Macarulla, Teresa , Babiker, Hani , Antonuzzo, Lorenzo , Melichar, Bohuslav, Kasi, Anup , Gang, Jin, Gallego, Javier , Hitre, Erika, Fouchardière, Christelle de la , Dragovich, Tomislav, Philip, Philip A. , Cutsem, Eric Van , Macarulla, Teresa , Investigators, on behalf of the PANOVA-3 Study, Spigel, David R. , Osipov, Arsen, Lou, Emil , Bullock, Andrea, Dragovich, Tomislav, Coveler, Andrew L. , Arena, Francis P. , Kasi, Anup, Ross, Sharona , Reeves, James, Green, Garrett, Uemura, Marc Isamu , Ye, Joseph, Wang, James Z. , Rausch, Daniel, Park, Jae‐Hyun , Schumaker, Robert, Gupta, Mukul, Letourneau, Richard, Fuchs, Martin , Vogel, Arndt , Chater, Jack, Schacher, Sabine, Stemmer, Salomon M. , Dourthe, Luis-Marie, Abdelghani, Méher Ben , Pons, Francesc Valladares, Guillén‐Ponce, Carmen , Yayá, Ricardo , Ponz‐Sarvisé, Mariano , Vincenzi, Bruno , Melichar, Bohuslav, Petruzelka, Lubos B. , Cutsem, Eric van, Borbath, Ivan , Hwang, Jun‐Eul , Oh, Sung Yong , Lee, Moon Hee , Choi, Hye Jin , Chon, Hong Jae , Ramlau, Rodryg , Mruk, Andrzej, Hitre, Erika, Bassam, Ali, Hao, Chunyi , Liang, Bo , Li, Wei , Bai, Chunmei , Joubert, Warren, Marx, Gavin M. , Azevedo, Srergio De, Hoff, Paulo M. , Vazquez, Arturo, Guerra, Cristian Chavez, Cortez, David Orta, Campos-Gómez, Saúl , Espinoza, Iván Romarico González

Journal of Clinical Oncology | May 31, 2025 | Volume: 43 | Issue: 21 | Pages: 2350-2360

10.1200/jco-25-00746 | PMID 40448572 Get It

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.
Gain of care independence following surgical intervention for cervical spondylotic myelopathy: a Quality Outcomes Database study
Bisson, Erica F. , Bydon, Mohamad , Asher, Anthony L. , Chan, Andrew K. , Wang, Michael Y. , Haid, Regis W., Knightly, John J. , Gottfried, Oren N., Shaffrey, Christopher I. , Virk, Michael S., Shaffrey, Mark E., Foley, Kevin T. , Coric, Domagoj , Upadhyaya, Cheerag D., Potts, Eric A. , Tumialán, Luis M. , Fu, Kai-Ming, Johnson, Sarah E. , Chou, Dean , Mummaneni, Praveen V. , Agarwal, Nitin , Virk, Michael S., Park, Paul , Lavadi, Raj Swaroop

Journal of Neurosurgery: Spine | May 30, 2025 | Volume: 43 | Issue: 2 | Pages: 170-180

10.3171/2025.2.spine231237 | PMID 40446343 Get It

OBJECTIVE Chronic spinal degenerative diseases have been associated with reduced quality of life and dependency on others for personal needs and care. The change between preoperative and postoperative care dependency has yet to be explored in patients with cervical spondylotic myelopathy (CSM). In this retrospective study of a prospectively collected database, the authors evaluated the return to independence in performing self-care following surgical intervention for CSM. METHODS The CSM dataset of the Quality Outcomes Database (QOD) Spine CORe study group was queried. Care dependency was assessed using the personal care component of the Neck Disability Index (NDI) questionnaire, having an ordinal scale from 0 to 5, with 5 representing the inability to independently perform activities of daily living. Numeric rating scale (NRS) scores for arm pain and neck pain were recorded at a 24-months postoperative follow-up. Multivariable logistic regression analyses were performed to identify baseline risk factors for an inability to care for oneself and the symptoms leading to care dependency at 24 months postoperatively. Satisfaction with surgery was measured using the 4-point North American Spine Society (NASS) index. RESULTS Of the 1137 patients with CSM and baseline personal care scores, 167 (14.7%) were care dependent at baseline (NDI personal care score ≥ 3). Patients with care dependency at baseline were predominantly Medicare beneficiaries and had a high school or lower level of education. Long-term follow-up rates for this study were 82.5% for NDI, 84.8% for patient satisfaction with surgery, 82.4% for NRS arm pain, and 81.8% for NRS neck pain. Of the care-dependent patients, more than 80% became independently able to care for themselves by the 24-month follow-up. Patients with resolved care dependency at 24 months had demonstrated lower baseline NDI and NRS neck pain scores (p < 0.01 for both). Neck pain was significantly associated with care dependency at 24 months’ follow-up (p < 0.01). Patients who reported improvement in their ability to care for themselves noted higher postoperative satisfaction (NASS score 1–2) at the 3-month (89.4% vs 80.2%, p < 0.01) and 24-month (88.2% vs 67.4%, p < 0.01) follow-ups. CONCLUSIONS Fifteen percent of patients with CSM depended on others for care preoperatively. After surgery to treat CSM, 81.8% of those who had depended on others for care became independent. Patients with improvements in care dependency noted higher postoperative satisfaction at the 3-month and 24-month follow-ups. Patients with resolved care dependency on long-term follow-up had lower NDI and NRS neck pain scores at baseline. Surgery had a significant impact on patients’ attainment of independence.
Immune checkpoint inhibitor (ICI) reuse after failure of first-line ICI in patients with metastatic dMMR/MSI gastrointestinal cancers: The INFLATE study.
Mercier, Léa , Overman, Michael J. , Alouani, Emily , Dutherage, Marie, Mazard, Thibault , Sclafani, Francesco , Montañá, Javier Ros, Guimbaud, Rosine , Pernot, Simon , Pietrantonio, Filippo , Auclin, Édouard , Hollebecque, Antoine , Lonardi, Sara , Sinicrope, Frank A. , Tougeron, David , Turpin, Anthony , Jayachandran, Priya , Palmieri, Lola‐Jade , Taı̈eb, Julien

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 3569-3569

10.1200/jco.2025.43.16_suppl.3569 Get It

3569 Background: Immune checkpoint inhibitors (ICIs) are a standard treatment for gastrointestinal (GI) cancers with mismatch repair deficiency (dMMR) or microsatellite instability (MSI). However, around 50% of patients develop resistance to ICIs, during treatment or after discontinuation. In these patients, the efficacy of reuse an ICI in patients progressing during a previous ICI (rechallenge), or in patients who progressed after discontinuation (reintroduction), remains unknown. The INFLATE study evaluates the efficacy of ICI reuse in patients who progressed on or after discontinuing ICI. Methods: This is a multicenter international retrospective study from the IMMUNODIG cohort, including patients from 34 centers in France, the United States, Italy, Belgium and Spain. All patients received ICI for dMMR/MSI GI cancer. We analyzed patients who had progressed following initial ICI (ICI-1) and subsequently received a rechallenge or a reintroduction with ICI (ICI-2), either monotherapy (mono-ICI) or biotherapy (bi-ICI). Results: A total of 77 patients were included, receiving bi-ICI (N = 34) or mono-ICI (N = 43) during ICI-2. The majority (76%) had a metastatic colorectal cancer. The reason for discontinuing ICI-1 was disease progression in 53% of cases, end of treatment in 15%, toxicity in 5% and other reasons in 26%. Patients who discontinued ICI-1 due to progression received MONO-ICI-2 in 29% of cases and BI-ICI-2 in 71%, whereas those who stopped for other reasons received MONO-ICI-2 in 86% and BI-ICI-2 in 14% of cases. Efficacy results are shown in Table 1. The ORR and DCR were 26% and 79% with MONO-ICI-2, and 16% and 71% with BI-ICI-2. Among patients who discontinued ICI-1 due to progression, BI-ICI-2 (N = 29) achieved an ORR and DCR of 8% and 65%, with a median PFS of 5.5 months (95%CI 4.07-10.4). These outcomes were 17%, 67%, and 3.7 months (95%CI 2.37-NA), respectively, with MONO-ICI-2 (N = 12). For patients who discontinued ICI-1 for reasons other than progression, BI-ICI-2 (N = 5) achieved an ORR and DCR of 60% and 100%, with a median PFS not reached (95%CI 11.5-NR), while MONO-ICI-2 (N = 31) achieved 29%, 82%, and 14.2 months (95%CI 11.2–NR), respectively. Conclusions: This is the first multicenter real-world study evaluating ICI reuse in dMMR/MSI GI cancers. In patients who discontinued ICI for reasons other than progression, reintroduction of ICI therapy upon progression achieves tumor control in 85% of cases. In cases of progression on mono-ICI, Bi-ICI re-challenge achieve tumor control in two-thirds of cases and might be to consider in some patients. ORR % DCR % PFS median (95%CI) OS median (95%CI) Overall N=77 21 76 7.65 months(5.5–11.5) 27.6 months(22.2–55.7) Discontinued ICI-1 due to Progression N=41 11 68 5.03 months(3.7–8.05) 26.7 months(21.1–NR) Discontinued ICI-1 for Other Reasons N=36 33 85 14.22 months(11.24–NR) 27.6 months(22.2–NR)
TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC).
Levy, Benjamin , Paz‐Ares, Luis , Herbert, Scott M., Yang, Tsung‐Ying , Lou, Yanyan , Zenke, Yoshitaka , Dómine, Manuel , Leventakos, Konstantinos , Horiike, Atsushi , Jia, Xiaoyu , Chiaverelli, Rachel, Goto, Yasushi , Lin, Chien‐Chung , Tolcher, Anthony W. , Cortinovis, Diego Luigi , Felip, Enriqueta , Calvo, Emiliano , Pan, Edward , Matsubara, Keisuke , Chisamore, Michael Jon

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 8501-8501

10.1200/jco.2025.43.16_suppl.8501 Get It

8501 Background: TROPION-Lung02 (NCT04526691) evaluated the TROP2-directed antibody-drug conjugate (ADC) Dato-DXd plus pembro combination with or without Pt-CT in aNSCLC. Here we report primary analyses of pts receiving combination therapy in the 1L setting. Methods: Pts across 6 cohorts were dosed with Dato-DXd (4 or 6 mg/kg) plus pembro 200 mg alone (doublet) or with pembro plus Pt-CT (triplet; cisplatin 75 mg/m 2 or carboplatin AUC 5) Q3W. PD-L1 expression (tumor proportion score) was assessed locally by immunohistochemistry (22C3 assay). Primary objectives were safety and tolerability; efficacy was a secondary objective. Results: As of Apr 29, 2024, 96 pts received either the doublet (n=42) or triplet (n=54) combination as 1L therapy; 29% and 15% of pts were ongoing, respectively. Median ages were 65 (doublet) and 64 years (triplet). Median treatment durations were 9.7 and 5.8 months, respectively. Stomatitis (doublet, 57%; triplet, 33%) and nausea (doublet, 42%; triplet, 48%), primarily Gr 1–2, were the most common adverse events (AEs) across both regimens. Treatment related serious AEs occurred in 5 (12%) and 12 (22%) pts in each cohort and no deaths related to study drug were seen. Efficacy outcomes, including by histology, are summarized in the Table. Biomarker analyses, including efficacy by PD-L1 status, will be presented. Conclusions: In this largest data set to date evaluating an ADC combined with an anti-PD-1/L1 agent in the 1L setting, the combination of Dato-DXd plus pembro treatment both with and without Pt-CT elicited durable antitumor activity in pts with aNSCLC. Tolerability of the combinations was as expected, based on known profiles of the individual agents. Clinical trial information: NCT04526691 . All 1L (n=96) 1L, Nonsquamous (n=75) 1L, Squamous (n=21) Response, n (%) Doublet (n=42) Triplet (n=54) Doublet (n=33) Triplet (n=42) Doublet (n=9) Triplet (n=12) Confirmed objective response rate 23 (55) 30 (56) 17 (52) 24 (57) 6 (67) 6 (50) Complete response 1 (2) 2 (4) 1 (3) 2 (5) 0 0 Partial response 22 (52) 28 (52) 16 (49) 22 (52) 6 (67) 6 (50) Stable disease 14 (33) 18 (33) 12 (36) 14 (33) 2 (22) 4 (33) Progressive disease 3 (7) 2 (4) 3 (9) 1 (2) 0 1 (8) Disease control rate a 37 (88) 48 (89) 29 (88) 38 (91) 8 (89) 10 (83) Median duration of response, mo (95% CI) 20.1 (9.7–NE) 13.7 (5.7–NE) 24.9 (9.7–NE) 18.0 (8.0–NE) 12.0 (5.5–NE) 5.5 (4.1–NE) Median PFS, mo (95% CI) 11.2 b (8.2–21.3) 6.8 c (5.5–11.1) 11.2 (6.1–21.3) 10.8 (5.5–17.3) 10.2 (0.4–NE) 6.7 (1.0–8.2) a Proportion of pts with confirmed CR + PR + SD at 12 wks. b.c Median (95% CI) PFS follow-up, mo: b 17.3 (11.3−26.8); c 23.5 (17.3−27.9). mo, months; NE, not evaluable.
Sex differences in chemotherapy completion and adverse events among patients with colon cancer (CALGB/SWOG 80702) (Alliance).
Cheng, En , Shields, Anthony F. , Shergill, Ardaman , Guthrie, Katherine A. , Couture, Félix , Kuebler, J. Phillip, Kumar, Pankaj , Tan, Benjamin , Krishnamurthi, Smitha , Ng, Kimmie , Philip, P. A., Shi, Qian , Kuang, Chaoyuan , Ma, Chao , O’Reilly, Eileen M. , Brown, Justin C. , Meyerhardt, Jeffrey A. , Cheng, En

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 3624-3624

10.1200/jco.2025.43.16_suppl.3624 Get It

3624 Background: Increasing chemotherapy completion and reducing chemotherapy adverse events (AE) are critical to improve survival after colon cancer diagnosis. Sex, as a biological variable, may impact chemotherapy treatment differently, and thus further investigation is needed to examine sex differences in chemotherapy completion and adverse events among patients with colon cancer. Methods: Among an NCI-sponsored trial conducted among patients with stage III colon cancer (CALGB/SWOG 80702), all patients received standard adjuvant chemotherapy FOLFOX (fluorouracil, leucovorin, and oxaliplatin). To signal chemotherapy completion, we utilized relative dose intensity (RDI) calculated as the ratio of the delivered dose intensity to planned dose intensity; and reduced RDI (RDI <85%) was considered as a clinically significant deviation from standard FOLFOX. From clinicians’ records of NCI’s Common Terminology Criteria for Adverse Events (CTCAE), we primarily focused on clinically significant AE such as neutrophils decrease, nausea, platelets decrease, hypertension, peripheral neuropathy, diarrhea, fatigue, gastritis, creatinine increase, gastric ulcer, myocardial ischemia, and cerebral ischemia; and severe AE was defined as the occurrence of any above AE with CTCAE grade ≥3. Using multivariable logistic regression that adjusted for body surface area (BSA) and other clinicopathological confounders, we estimated adjusted odds ratios (OR) for the associations of sex with reduced RDI and severe AE. Results: Of 2201 patients, mean (standard deviation [SD]) age was 60.9 (10.9) years, 1019 (46.3%) were female, 1750 (79.5%) were White, 172 (7.8%) were Hispanic, 964 (43.8%) experienced reduced RDI, and 1156 (52.5%) had severe adverse events. Compared to males, females were at significantly higher risks of experiencing reduced RDI (OR [95% CI]: 1.57 [1.27-1.93], P <0.001) and severe AE (OR [95% CI]: 1.73 [1.41-2.12], P <0.001). Conclusions: Our findings suggested females are more likely than men to experience reduced RDI and severe AE during colon cancer chemotherapy. Clinical Impact: In the era of precision medicine, sex (as a biological variable) should be considered in optimizing colon cancer chemotherapy to improve completion and reduce toxicities. Clinical trial information: NCT01150045 .
Serum estradiol (sE2) levels in premenopausal (PreM) women receiving neoadjuvant ovarian function suppression (OFS) with the oral SERD amcenestrant, alone, or in combination with letrozole or abemaciclib in the I-SPY2 Endocrine Optimization Pilot (EOP).
Chien, Jo, Norwood, Peter, Wei, Mei , Chen, Nan , Borowsky, Alexander D. , Melisko, Michelle , Mukhtar, Rita A. , Giridhar, Karthik V. , Goetz, Matthew P. , Vaklavas, Christos , Elias, Anthony , Rugo, Hope S. , Swigart, Lamorna Brown , Shatsky, Rebecca , Huppert, Laura Ann , Esserman, Laura J.

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 604-604

10.1200/jco.2025.43.16_suppl.604 Get It

604 Background: The addition of OFS to standard endocrine therapy (ET) improves iDFS for preM women with early-stage hormone receptor positive (HR+) breast cancer (BC). Incomplete OFS occurs in a subset of women, the long-term clinical significance of which is unclear. This study evaluates local sE2 levels in preM women receiving OFS with an oral SERD in the neoadjuvant (NA) setting. Methods: The EOP is a I-SPY2 sub-study investigating NA endocrine-based strategies in pts with HR+ HER2- Stage 2/3 BC predicted to have lower benefit from chemotherapy. Pts were randomized to oral amcenestrant 200 mg/d, alone or in combination with either letrozole 2.5 mg/d or abemaciclib 150 mg bid. Additional pts were randomized to a standard of care (SOC) arm consisting of an aromatase inhibitor. All PreM pts received OFS with monthly GnRHa up to 2 wks prior to C1D1 of study therapy. Pts were treated for 6 months prior to surgery. sE2 levels were collected locally prior to each GnRHa injection. Tumor Ki67 was assessed at 3 weeks and surgery, and associated with sE2 level. Statistical significance was determined using a two-sided Student’s t-test and a significance level 0.05. Results: Between 5/2021-8/2022, 74 pts were enrolled to an amcenestrant containing arm, 40 of whom were preM. 38/40 pts had at least one local sE2 level measured in follow up. Of these 38 pts (median age 45 years), 37 suppressed sE2 into the postmenopausal (postM) range at one or more follow-up timepoints. Of the 37 pts that completely suppressed into the postM range, 6 pts had sE2 levels rebound into the preM range (mean 319 pg/mL, range 20-848 pg/mL) with peak sE2 levels occurring at a median of 12 weeks from C1D1. One pt never suppressed to the postM range (peak sE2 1227 pg/mL) and was found to have an ovarian cyst after 3 months on amcenestrant, requiring surgery. One additional pt had multiple ovarian cysts (sE2 84 pg/mL). Median age of the 7 pts who had sE2 rebound was 43 years. There was no significant difference in Ki67 at 3 weeks and surgery between pts whose sE2 levels remained suppressed (median Ki67 2.0%) compared to those whose estradiol rebounded into the preM range or never suppressed (median Ki67 1.5%). In the 5 pts whose sE2 rebounded to > 200 pg/mL, all pts had tumor Ki67 < 10% at 3 weeks and surgery. Between 12/2022 and 8/2023, 20 pts were enrolled to AI +/- OFS and 11 pts were preM. Of the 11 preM pts, all pts suppressed sE2 to the postM range. No SOC patients had sE2 levels rebound into the preM range. Conclusions: In this study of neoadjuvant oral SERD with monthly OFS, 7/38 (18.4%) preM pts had sE2 levels remain or rebound into the preM range. sE2 levels did not appear to impact Ki67 suppression on NA ET. Work up for ovarian cysts should be considered in pts with symptoms, or significantly elevated or persistent sE2 levels. Clinical trial information: NCT01042379 .
I-SPY2 endocrine optimization pilot (EOP): Neoadjuvant lasofoxifene (Laso) in molecularly selected patients with hormone receptor positive (HR+)/HER2 negative (HER2-) stage 2/3 breast cancer (BC).
Wei, Mei , Veer, Laura van ‘t , Alkhafaji, Silver , Hirst, Gillian L. , Chen, Nan , Borowsky, Alexander D. , Chien, Jo, Hirst, Gillian L , Elias, Anthony , Giridhar, Karthik V. , Goetz, Matthew P. , Mukhtar, Rita A. , Vaklavas, Christos , Veer, Laura J. van’t , Rugo, Hope S. , Symmans, W. Fraser , Swigart, Lamorna Brown , Onishi, Natsuko , Yee, Douglas , Hylton, Nola M. , Esserman, Laura J.

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 612-612

10.1200/jco.2025.43.16_suppl.612 Get It

612 Background: EOP, an I-SPY2 sub-study, evaluates the tolerability and activity of novel endocrine strategies in stage 2/3 breast cancer (BC) patients (pts) predicted to have lower chemotherapy benefit. Laso, a selective estrogen receptor modulator (SERM), has shown favorable toxicity profile and activity in HR+/HER2- endocrine-resistant metastatic BC. Methods: Pts with Stage 2/3 HR+/HER2-, MammaPrint (MP) low risk BC were enrolled. Pts with MP High1 BC were included if clinically node-negative. Pts received oral laso 5 mg daily for six 28-day cycles. Laso was continued until the day prior to surgery. Premenopausal pts received ovarian function suppression (OFS) starting C2D1. The primary endpoint was feasibility (>75% of patients completing >75% study therapy). Baseline (T0), 3-wk (T1) biopsies, and the surgical specimen (T3) was assessed centrally for Ki-67. Breast MRI functional tumor volume (FTV) was performed at T0, T1, 12 weeks (T2), and pre-operatively (T3). Blood was collected for tumor informed ctDNA at T0, T1, T2, T3. Advance event (AE) was assessed using CTCAE V5. Results: From 3/2023 to 5/2024, 20 pts were enrolled. Median age 50.5 years, 50% premenopausal, and 1 male pt. 60% cN0, 80% MP low-risk signature. 18 (90%) pts completed >75% study therapy. Two pts discontinued treatment due to pt preference. Median Ki67 at T0 was 14.7%. At T1, 87.5% of pts remained or suppressed Ki67 to <10% and 37.5% suppressed to <2.7%. Ki67 at T1 was similar between pre-and postmenopausal pts despite OFS (Table). The median MRI FTV was 8.4 cc at T0, and 3.4 cc at T3. Median % FTV reduction from T0 to T3 was -47.5%. 2/20 pts (10%) achieved a modified PEPI score of 0. No patients achieved completed pathological response. Of the 16 pts with RCB results, 2 (12.5%) RCB-1, 6 (37.5%) RCB-2, 8 (50%) RCB-3 disease. 14 pts had ctDNA available at T0. 4/14 were ctDNA+ at T0, 2 of whom became ctDNA negative, and 2 remained ctDNA+. 10/14 pts were ctDNA negative at T0, 8 of whom remained negative, 2 became positive at T1 then cleared. All AEs were grade(G) 1 except 1 pt with G2 hot flashes. Most common AEs include hot flashes (85%), constipation (50%), fatigue (50%), and nausea (35%). One pt had G3 hypersensitivity and hypertension, both unrelated to therapy. Conclusions: Neoadjuvant laso demonstrates a favorable AE profile and promising anti-tumor activity in suppressing 3-wk Ki67 and MRI FTV change in pts with HR+ HER2-negative early BC. Ki67 suppression in premenopausal pts was seen in the absence of OFS. Clinical trial information: NCT01042379 . Ki67 expression at pre-treatment, and 3-wk time point. All Patients(n=20) Premenopausal (n=10) Postmenopausal (n=9) Median Ki67 expression Baseline 10.0% 12.5% 10.0% 3-wk 5.1% 3.0% 6.0% Number of pts with Ki67 expression <10% at 3-wk 87.5% 1 87.5% 85.7% Number of pts with Ki67 expression <2.7% at 3-wk 37.5% 50% 28.6% 1 Include the one male pt.
The role of income and rurality in US cancer mortality: A SEER analysis.
McGovern, Emily , Swenson, Abigail Paige, Williams, Aquino Anthony, Deviley, Jake A. , Eldien, Anika , Armstrong, Andrew , Prakash, Sahil, Gully, Brooke , Kelso, S. R., Jacobson, Ingrid , Swenson, Wade T. , Schroeder, Zachary, Williams, Aquino Anthony, Prakash, Sahil, Kelso, Sean, Pritchett, Joshua C.

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e13828 Get It

e13828 Background: Disparities in cancer outcomes between rural and urban populations are often linked to limited healthcare resources in rural areas. However, the impact of socioeconomic factors, particularly income inequality, requires further investigation. Methods: We analyzed cancer mortality rates using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on rural-urban continuum codes and median county income, the proportions of patients with de novo metastatic disease at diagnosis, those aged 80 and older, and those experiencing a treatment delay of three months or more. Results: Our findings indicate that non-metropolitan counties (56.7%, 95% CI: 56.6%, 56.8%) and those with lower median incomes (54.9%, 95% CI: 54.8%, 55.1%) have significantly lower cancer survival rates than metropolitan counties (62.6%, 95% CI: 62.5%, 62.6%) and higher-income rural counties (62.6%, 95% CI: 62.6%, 62.7%), a trend consistent over the observation period. Higher proportions of de novo metastatic disease and increased treatment delays were observed in counties with lower income and greater rurality, with these counties also demonstrating higher annual percentage rates of change for both de novo metastatic disease (P < 0.05) and treatment delays (P < 0.05). Conclusions: Lower county-level median household income is associated with higher cancer mortality rates, increased de novo metastatic disease, and longer treatment delays. These results underscore the need to appreciate the role of income disparities in cancer outcomes and to improve access to oncology care in underserved rural populations.