bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor treatment (HARMONi-A): A randomized, double-blind, multi-center, phase 3 trial.
Authors: Zhang Li , Fang Wenfeng , Zhao Yuanyuan , Luo Yongzhong , Yang Runxiang , Huang Yan , He Zhiyong , Zhao Hui , Li Mingjun , Li Kai , Song Qibin , Du Xiaobo , Sun Yulan , Li Wei , Xu Fei , Wang Zhiyu , Yang Kunning , Fan Yun , Li Wenting , Xia Yu 
Published: June 2024

8508 Background: Ivonescimab (AK112/SMT112) is a anti-PD-1/VEGF bispecific antibody. Previous phase I/II clinical studies have shown potential efficacy of ivonescimab in NSCLC patients with EGFR mutations who had failed prior EGFR-TKIs therapies. This phase 3 study aimed to evaluate and confirm the efficacy and safety of ivonescimab combined with chemotherapy versus chemotherapy alone in this population. Methods: Patients were randomized 1:1 to receive ivonescimab (20 mg/kg) plus pemetrexed (500 mg/m2) and carboplatin (AUC 5) or placebo plus chemotherapy once every 3 weeks for four cycles, with stratification according to the third-generation EGFR-TKI (received vs not received) and brain metastases (presence vs absence), followed by maintenance therapy of ivonescimab and pemetrexed or placebo and pemetrexed. The primary endpoint was progression-free survival (PFS) in intention-to-treat (ITT) population assessed by independent radiographic review committee (IRRC) per RECIST v1.1. Here we report the results of the first planned interim analysis. Results: Total 322 patients were randomized (161 to the ivonescimab plus chemotherapy arm, 161 to the placebo plus chemotherapy arm). 86.3% versus 85.1% of patients had received the third generation EGFR-TKIs treatment, 21.7% versus 23.0% of patients had brain metastases. As of March 10, 2023, median follow up time was 7.89 months. PFS was significantly improved in the ivonescimab plus chemotherapy arm (HR 0.46 [0.34, 0.62], P < 0.0001). Median PFS (95%CI) by IRRC were 7.06m (5.85, 8.74) in the ivonescimab arm versus 4.80m (4.21, 5.55) in chemotherapy arm. The prespecified subgroup analysis showed PFS benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including in patients who progressed on the third-generation EGFR-TKIs therapy (HR 0.48, 95% CI 0.35-0.66), those with brain metastases (HR 0.40, 0.22-0.73), those with EGFR mutation of deletion 19 (HR 0.48, 0.32-0.73), and individuals with T790M mutation positive (HR 0.22, 0.09-0.54). The ORR were 50.6% and 35.4%, respectively. Grade ≥3 TEAEs occurred in 99 (61.5%) patients versus 79 (49.1%) patients, the most common grade ≥3 TEAEs were chemotherapy related adverse events. Grade ≥3 immune-related adverse events occurred in 10 (6.2%) patients versus 4 (2.5%). Grade ≥3 VEGF blocking related adverse events occurred in 5 patients (3.1%) versus 4 patients (2.5%). Conclusions: Ivonescimab plus chemotherapy significantly improved PFS while maintaining a manageable safety profile in patients who had failed EGFR-TKIs treatments. Clinical trial information: NCT05184712 .
Safety and efficacy of osimertinib plus consolidative stereotactic ablative radiation (SABR) in advanced EGFR mutant non-small cell lung cancer (NSCLC): Results from a multi-center phase II trial.
Authors: Rashdan Sawsan , Sampath Sagus , Iyengar Puneeth , Dowell Jonathan , Ahn Chul , Westover Kenneth D. , Zhang Yuanyuan , Cole Suzanne , Massarelli Erminia , Amini Arya , Koczywas Marianna , Gerber David E 
Published: June 2024

8518 Background: Despite high response rates to EGFR inhibitors, patients with advanced EGFR mutant NSCLC generally experience disease progression within two years (osimertinib median PFS 18.9 months, median OS 38.6 months). We sought to determine whether administration of SABR to residual sites of disease at the time of expected best response to EGFR inhibition could prolong disease control. Methods: This was a multi-center single-arm phase 2 study. Eligible patients had advanced EGFR mutant (exon 19 or 21) NSCLC not restricted by number, site, or size of metastases; ECOG 0-2; no prior treatment with EGFR inhibitors or immune checkpoint inhibitors; and no history of interstitial lung disease. Patients with stable or responding disease after 8 weeks of osimertinib received SABR to persisting lesions, followed by continued osimertinib until progression or intolerance. At subsequent progression, patients could receive further SABR and continue osimertinib if deemed clinically feasible and appropriate. The primary endpoint was progression-free survival (PFS); secondary endpoints included duration on osimertinib, toxicity, and overall survival (OS). Results: A total of 43 patients (32 women, 11 men) were enrolled and initiated osimertinib, of whom 29 (67%) received SABR. Reasons SABR was not administered included inadequate response (9%), insufficient residual disease (19%), and other (5%). At a median follow-up of 35.7 months (95% CI, 28.8, 37.6), 42 evaluable patients had a median PFS of 32.6 months and a median OS of 45.7 months. The median duration of osimertinib was 31.5 months. Grade ≥3 toxicities included one incidence each (2%) of the following: pain at the site of radiation, paronychia, liver enzyme elevation, fatigue, hyponatremia, diarrhea, and pneumonitis. Conclusions: Osimertinib plus consolidative SABR appears to provide a PFS and OS benefit when considered against historical data with osimertinib alone. This treatment strategy may offer a well-tolerated and practical approach to improving outcomes for patients with advanced EGFR mutant NSCLC. Clinical trial information: NCT03667820 .
Intracranial efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously treated advanced/metastatic non-small cell lung cancer (a/m NSCLC) with actionable genomic alterations (AGA): Results from TROPION-Lung05.
Authors: Lisberg Aaron , Ahn Myung-Ju , Kitazono Satoru , Cho Byoung Chul , Blumenschein George R. , Shum Elaine , Pons-Tostivint Elvire , Goto Yasushi , Yoh Kiyotaka , Paz-Ares Luis G. , Heist Rebecca Suk , Baas Paul , Planchard David , Perol Maurice , Felip Enriqueta , Su Wu-Chou , Zebger-Gong Hong , Lan Lan , Liu Chelsea , Sands Jacob 
Published: June 2024

8593 Background: Brain metastases (mets) occur frequently in pts with NSCLC, particularly pts with certain AGAs, and indicate poor prognosis. For pts with AGAs, treatment options are limited once targeted therapy and platinum-based chemotherapy (Pt-CT) become ineffective. The phase 2 TROPION-Lung05 trial (NCT04484142) of Dato-DXd has demonstrated systemic efficacy and a manageable safety profile in heavily pretreated pts with a/m NSCLC with AGAs who progressed following targeted therapy and Pt-CT; here we report an exploratory analysis of intracranial (IC) efficacy. Methods: Pts were treated with Dato-DXd 6 mg/kg IV Q3W. Pts with clinically stable brain mets were eligible. IC responses were assessed by blinded independent central review (BICR) of cranial CT/MRI (CNS BICR; per CNS RECIST) at baseline (BL) and Q6W. Systemic objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR, defined as CR+PR+SD or non-CR/non-PD lasting ≥6 mo), progression-free survival (PFS) by BICR per RECIST 1.1 and treatment-related adverse events (TRAEs) were determined in pts with and without BL brain mets. Results: In total 53/137 (39%) treated pts had BL brain mets; 29/53 (55%) had an EGFRmutation. Pts with BL brain mets had a median (range) of 3 (2–6) prior systemic therapies in the a/m setting, including targeted therapy and Pt-CT with/without immune checkpoint inhibitors; 15/53 (28%) had untreated brain mets. At data cutoff (Dec 14, 2022), median (range) study and treatment durations among pts with BL brain mets were 14.8 (9.7–20.5) and 3.2 (0.7–17.2) mo, respectively. Of these pts, 18/53 (34%) had measurable IC target lesions (3 untreated) and 35/53 (66%) had only non-target IC lesions. In 18 pts with target lesions, IC ORR was 22% (95% CI, 6–48), including 1 of 3 pts with untreated target lesions; IC DCR was 72% (95% CI, 47–90); IC CBR was 44% (95% CI, 22–69). Reduction in the sum of diameters of brain lesions was seen in 10/18 (56%). Median time to IC response was 1.5 (range, 1.3–5.4) mo; median duration of IC response was 5.5 (95% CI, 3.4–NE) mo Systemic efficacy and safety were similar in pts with and without BL brain mets (Table). Conclusions: Dato-DXd showed encouraging IC activity consistent with systemic responses in pts with a/m NSCLC with AGAs, supporting further investigation of Dato-DXd in pts with brain mets. Clinical trial information: NCT04484142 . [Table: see text]
Safety and efficacy of ifebemtinib (IN10018) combined with D-1553 in non-small-cell lung cancer (NSCLC) with KRAS G12C mutation: Results from a phase Ib/II study.
Authors: Song Zhengbo , Li XingYa , Lin Rongbo , Yuan Yuan , Shi Huaqiu , Liu Ying , Luo Yongzhong , Lv Tangfeng , Zhang Yiping , Zhu Yinxin , Wang Zaiqi 
Published: June 2024

8605 Background: KRAS G12C mutation is present in about 12-14% of NSCLC population. Ifebemtinib (IN10018) is a highly potent and selective oral inhibitor of focal adhesion kinase (FAK). D-1553 (garsorasib) is a novel oral and potent KRAS G12C inhibitor. Preclinical data showed that ifebemtinib in combination with KRAS G12C inhibitors had synergistic anti-cancer effect in multiple KRAS G12C mutant cancer models. This study is to evaluate the safety and antitumor activity of ifebemtinib combined with D-1553 in solid tumors with KRAS G12C mutation. Here we report the preliminary data from phase II part of front-line NSCLCs with KRAS G12C mutation. Methods: Locally advanced or metastatic NSCLC subjects without prior systemic anti-cancer therapy were enrolled. Subjects were required to have KRAS G12C mutation in tumor tissues. All subjects were assigned to the recommended phase II dose (RP2D) of ifebemtinib (100mg qd) + D-1553 (600mg bid). Results: As of 31 January 2024, 33 front-line NSCLC subjects with KRAS G12C mutation were enrolled and received the combination therapy. Median age was 65yrs (range 58, 83), 93.9% were male, and 81.8% had stage IV metastatic disease. Median study follow-up (FU) was 2.2 months (range 1.1, 9.2). The safety profile of the combination therapy is comparable to each single agent without additive toxicities. No ifebemtinib- or D-1553-related death was reported. Four subjects (12.1%) had ifebemtinib-related SAEs (diarrhea, enteritis, oedema peripheral and proteinuria) as assessed by investigators, and all SAEs were also considered D-1553 related. Six subjects (18.1%) had ≥ Grade 3 ifebemtinib-related AEs as assessed by investigators, and all were also D-1553 related AEs. The majority of ifebemtinib-related AEs were CTCAE Grade 1 or 2. There was no event leading to study treatment discontinuation. We have observed continuing tumor shrinkage in almost all subjects who had at least 2 tumor assessments. Among 16 subjects with ≥ 3 months FU, preliminary efficacy found that 14 had best overall response of partial response (PR) including 12 confirmed PRs and 2 unconfirmed but still in treatment, 1 had stable disease (SD), and 1 had progressive disease (PD). The overall response rate (ORR) was 87.5% (95%CI: 56.6, 96.2), and disease control rate (DCR) was 93.8% (95%CI: 63.6, 98.5). The median duration of response (DOR), median progression-free survival (PFS) and overall survival (OS) have not been reached. Conclusions: The combination of ifebemtinib and D-1553, as a dual-oral regimen, showed promising antitumor activity and manageable safety profile in KRAS G12C mutant front-line NSCLC population. Long term follow-up is needed to assess the potential of such novel combo. Clinical trial information: NCT06166836 ; NCT05379946 .
Bevacizumab in combination with chemotherapy for treating patients with advanced RET+ non-small cell lung cancer.
Authors: Aldea Mihaela , Marinello Arianna , Monnet Isabelle , de Saint Basile Hortense , Cousin Sophie , Duruisseaux Michaël , Calles Antonio , Metro Giulio , Zugazagoitia Jon , Massa Giacomo , Gomez Patricia , Tabbò Fabrizio , Russo Alessandro , Fallet Vincent , Lindsay Colin R , Bria Emilio , Eisert Anna , Guisier Florian , Planchard David , Besse Benjamin 
Published: June 2024

8647 Background: RET inhibitors (RETi) are currently the preferred first-line treatment in advanced RET fusion-positive (RET+) non-small cell lung cancer (NSCLC). Despite impressive efficacy of RETi, resistance is inevitable, and the optimal therapy beyond RETi remains unclear. Immunotherapy has shown limited efficacy in these patients. This study aims to investigate the impact of adding bevacizumab to chemotherapy regimens on treatment outcomes. Methods: This multicenter, retrospective study included patients with RET+ advanced NSCLC who received either a platinum-doublet chemotherapy (D) (+/-anti-PD-L(1) agents (ICB)) or a non-platinum monotherapy (M), with or without bevacizumab (Bev). Non-platinum agents were limited to pemetrexed, paclitaxel, or docetaxel. Only the first administration of the regimen was considered. Objective responses (OR), progression-free survival (PFS), and overall survival (OS) from the start of treatment were compared between patients receiving and not receiving Bev. Results: Of 185 patients, 20 received Bev in doublet chemotherapy (D+Bev, none with ICB) and 165 did not (D, 68 with ICB). Additionally, 40 underwent single-agent chemotherapy, with 8 on Bev (M+Bev) and 32 without (M). D+Bev patients were younger (median age: 54 vs. 61 years, p=0.026), less often treated with RETi (55% vs. 79%, p=0.023), with no other demographic or disease-related group differences. Both D+Bev and D had a median of 1 treatment line [IQR 1-1]. M+Bev and M had a median of 3 and 2 treatment lines, respectively (p=0.3), and numerically more M+Bev patients had brain metastases (25% vs. 13%, p=0.6). In the D+Bev vs D (+/-ICB) comparison, the OR was 55% vs 47% (p=0.7), and the median PFS was significantly longer in the D+Bev group (17 months vs. 8.8 months, p=0.018). When comparing D+Bev with D+ICB, D+Bev still showed a significant advantage in median PFS (17 months vs 9.7 months, p=0.05). The median OS was 51.4 months for D+Bev compared to 38.7 months for D (p=0.89). Multivariate analysis revealed that Bev use was independently associated with longer PFS (hazard ratio [HR] 0.4, p=0.01), while ECOG>1 (HR 4.3, p<0.0001) and male sex (HR 1.7, p=0.01) were associated with shorter PFS. In the M+Bev versus M group, the OR was 13% versus 25% (p=0.6), median PFS was 2.4 months versus 4.1 months (p=0.06), and median OS was 12.1 months versus 39 months (p=0.06). Conclusions: Bevacizumab with platinum-doublet chemotherapy seems to outperform platinum-doublet with or without ICB in progression-free survival. Prospective research is needed to evaluate the extent of bevacizumab's benefit for RET+ NSCLC.
Decision making in oncology: Unleashing the power of artificial intelligence—Beyond the question of feasibility.
Authors: Gil Deza Ernesto , Garcia Gerardi Carlos , Gil Deza Lourdes , Abal Mariana , Smolje Leonel , Jaunarena María del Huerto , Tognelli Flavio A , Norese Gabriela , Martin Reinas Gaston , Gercovich Daniela 
Published: June 2024

9021 Background: This study examines how consulting artificial intelligence (Chat GPT, Bard) or electronic tools (Apps, Journal or Guidelines) affects the decision-making process in Oncology Fellows. Methods: In the OSCE IOHM-USAL 2023, Oncology Fellows (2022 and 2023 cohorts) individually answered stations I and II, both spontaneously and after AI consultation. Group responses for stations III and IV were also gathered. Sign tests compared pre- and post-consultation responses in stations I and II while the impact of AI in stations III and IV was individually assessed on a five-point scale (0= Null and 5= Extremely useful). Results: 15 Oncology Fellows participated in OSCE 2023- 14 Females. Median age: 30 (r=28-36). A) Stations I - II Cases: Case1: 70 y. Non smoker. PS 0. Stage IV NSCLC. PS 0. EGFR mutated E746 _A750. PDL1 90%. Case 2: 52 y. Postmenopausal Stage II Luminal B Her2 negative Breast cancer (pT2, pN1, M0). Case 3: 35 yo. Advanced colon cancer. Stage IV. BRAF p(V600E) c.1799 A>C. No Micorsatellite Instability. B) Station III (Ethics Committee), the following cases were addressed: 4. “BRCA1: Insured, not excluded”. 5. “Smoke vs. oath? Tough choice” 6. “Follow Lynch path, or HMO exit”. In all three cases, 3/15 students reported finding AI useful in the discussion. C) Station IV (Tumor board), the following cases were addressed: 7. “Postmenopausal NOS IBC (pT1c pNmic Luminal B Her2 negative)”. 8. “Oncology emergency in a 22 y male patient testicular tumor pending pathology”. In Case 7, 3/15 students reported finding AI useful in the discussion. In Case 8, 4/15 students reported finding AI useful. Conclusions: 1. A study of 15 oncology fellows found no appreciable influence of AI on clinical decision-making. 2. Analysis of eight cases (individual/collective) identified anchor value, optimistic denial, and confirmation bias in reasoning and processing. 3. Fellow training in critical AI analysis and outcome evaluation is imperative. [Table: see text]
Roll out and influence of an educational program: Talking about risk, uncertainties of testing in genetics (TRUSTING).
Authors: Jenkins Valerie A. , Habibi Ruth , Hall Virginia , Leonard Pauline , Lawn Annaliese , Naik Jay , Papps-Williams Rachel , Fallowfield Lesley 
Published: June 2024

9025 Background: Family history clinics face significant capacity issues making calls for genetic testing of all breast cancer (BC) patients problematic. Mainstreaming of services by health care professionals (HCPs) is needed but many lack confidence and familiarity with genetic counseling. Following successful development and evaluation of the TRUSTING educational program (Fallowfield et al. BJC 2022), facilitators were trained to roll out workshops for BC HCPs. Here we report the workshops’ effect on participants’ knowledge, skills, and self-confidence and influence on mainstreaming. Methods: 1 surgeon, 3 oncologists, 1 nurse specialist facilitated the 8-hr program in pairs. Workshop content included didactic components to enhance knowledge and various exercises to promote self-awareness about individual participants’ tolerance to uncertainty and risk. Groups discussed 6 filmed scenarios showing interactions between surgeons and geneticists with the proband (triple negative BC and BRCA2 pathogenic gene alteration), her sister (BRCA2 +) and their anxious cousin (BRCA2 -). Pre-workshop, participants completed: - 1) an 18-item multiple choice knowledge questionnaire about gene testing in breast cancer 2) a 9-item questionnaire exploring self-confidence when discussing/advising patients about different aspects of BRCA testing, results, and treatments and 3) an Intolerance to Uncertainty Scale. Knowledge and self-confidence together with general feedback questions about overall satisfaction with facilitators and the event were assessed post workshop. Follow-up questionnaires sent 3-12 mths later examined the impact TRUSTING workshops had made on participants’ own practice and implementation of mainstreaming in their clinic. Results: 120 participants (61 surgeons; 41 nurses; 9 oncologists; 9 other) attended 12 UK workshops. There were improvements post workshop in knowledge (mean change = 6.57; 95% CI 5.97 to 7.16; p<0.001) and self-confidence (mean change = 2.64; 95% CI 2.33 to 2.95; p<0.001). Feedback about the facilitators’ approach was uniformly high (mean range 9.65 to 9.90 /10). Most found workshops useful, enjoyable, and informative; 98% would definitively recommend them to colleagues. Follow up data revealed that attendance significantly impacted individuals’ own practice with 59% reporting it had improved their discussions about genetic testing with patients. When asked about mainstreaming more generally 81% reported it as “OK” or “working very well”, others (16%) that it had not yet started or (3%) that it was problematic. Conclusions: Discussing the implications of pathogenic gene alterations on patients’ treatment and risk-reducing interventions is complex when patients are already coming to terms with a BC diagnosis. The TRUSTING educational program is an effective means of helping HCPs now involved in the mainstreaming of genetic testing.
Training of clinical oncologists in Africa: Results of a regional survey.
Authors: Okwunze Franklin Kenechukwu , Yesufe Abdu Adem , Abdou Aalaa Mahmoud Hassan , Omoleye Olasubomi Jimmy , Senyuy Wah Praise , Grover Surbhi , Anakwenze Chidinma Pamela 
Published: June 2024

9026 Background: Africa grapples with a significant human resource shortage in cancer care. The vast majority of practicing oncologists are clinical oncologists, performing the roles of both medical and radiation oncologists. Building a sustainable oncology workforce depends on robust training pipelines. However, the distribution and characteristics of oncology training programs across the continent have not been described. Methods: A cross-sectional study was conducted to outline the landscape of postgraduate clinical oncology training in Africa. A semi-structured electronic questionnaire designed to collect data on locations and capacity of training centers, components of training curriculum, and administration of training programs was distributed via e-mail between February and May 2023 to board-certified clinical oncology consultants practicing in Africa. Participants were identified through the personal contacts of the co-authors. Results: Responses were received from 31 oncologists practicing in 24 countries. We identified 74 centers in 16 countries (67%) with ongoing clinical oncology training, and Egypt, South Africa, and Tunisia accounted for two-thirds of all training centers identified. Duration of training ranged from 4 to 8 years. Each year, about 230 residents commence training, and 198 graduate from training and join the workforce. More than half of the countries with available data require an internship and passing an entrance examination before commencing training. Almost all countries require trainees to pass an exit examination and submit a thesis before completing training. We obtained data on training components in 19 (26%) centers, and all centers provide training in chemotherapy administration and radiotherapy techniques. However, marked variations were observed in the exposure to modern radiotherapy techniques, with 10 (53%) centers including IGRT and 5 (26%) including IMRT. More than three-quarters of respondents reported that most trainees find jobs in the government service after completing training. Conclusions: Clinical oncology training programs in Africa are relatively limited in number. Moreover, there is a wide variation in the existing programs in terms of training duration and components of curriculum. There is tremendous potential for expansion to countries without training, which can be facilitated by partnerships with existing training programs on the continent. Furthermore, regional coordination and accreditation is vital to ensure uniformity.