Institution Of Engineers Research Articles

Assessment of a hybrid solar water heating system: environmental impact and economic viability

ABSTRACT Conventional methods of space heating are not only expensive but also environmentally harmful, as they emit greenhouse gases that contribute to global warming. To tackle this issue, a hybrid solar water heating system assisted by a solar evacuated tube collector has been developed at the Madhav Institute of Technology and Science in Gwalior, India. Experiments conducted from November to February 2022–23 (winter season) revealed promising results. Throughout the winter season, the system achieved a daily average effective solar heat collection of 2.85 kWh, with a daily average collector efficiency of 45.5%. The average coefficient of performance (COP) of the solar water heat exchanger was 3.5. Additionally, the system demonstrated an energy payback time of 1.2 years, shorter than that of conventional systems. Over its lifetime, the developed winter heating system is estimated to mitigate 127.9 tonnes of CO2 emissions, earning a carbon credit of $1408. Economic analysis further revealed a favorable benefit-to-cost ratio for the hybrid system, ranging from 3.13 to 3.36, with a payback period varying from 5.03 to 4.47 years for an inflation rate of 6–13%. These findings affirm the feasibility and efficacy of a solar-powered hybrid active winter heating system.

Enhancing Ethiopian power distribution with novel hybrid renewable energy systems for sustainable reliability and cost efficiency

Economic development relies on access to electrical energy, which is crucial for society’s growth. However, power shortages are challenging due to non-renewable energy depletion, unregulated use, and a lack of new energy sources. Ethiopia’s Debre Markos distribution network experiences over 800 h of power outages annually, causing financial losses and resource waste on diesel generators (DGs) for backup use. To tackle these concerns, the present study suggests a hybrid power generation system, which combines solar and biogas resources, and integrates Superconducting Magnetic Energy Storage (SMES) and Pumped Hydro Energy Storage (PHES) technologies into the system. The study also thoroughly analyzes the current and anticipated demand connected to the distribution network using a backward/forward sweep load flow analysis method. The results indicate that the total power loss has reached its absolute maximum, and the voltage profiles of the networks have dropped below the minimal numerical values recommended by the Institute of Electrical and Electronics Engineers (IEEE) standards (i.e., 0.95–1.025 p.u.). After reviewing the current distribution network’s operation, additional steps were taken to improve its effectiveness, using metaheuristic optimization techniques to account for various objective functions and constraints. In the results section, it is demonstrated that the whale optimization algorithm (WOA) outperforms other metaheuristic optimization techniques across three important objective functions: financial, reliability, and greenhouse gas (GHG) emissions. This comparison is based on the capability of the natural selection whale optimization algorithm (NSWOA) to achieve the best possible values for four significant metrics: Cost of Energy (COE), Net Present Cost (NPC), Loss of Power Supply Probability (LPSP), and GHG Emissions. The NSWOA achieved optimal values for these metrics, namely 0.0812 €/kWh, 3.0017 × 106 €, 0.00875, and 7.3679 × 106 kg reduced, respectively. This is attributable to their thorough economic, reliability, and environmental evaluation. Finally, the forward/backward sweep load flow analysis employed during the proposed system’s integration significantly reduced the impact of new energy resources on the distribution network. This was evident in the reduction of total power losses from 470.78 to 18.54 kW and voltage deviation from 6.95 to 0.35 p.u., as well as the voltage profile of the distribution system being swung between 1 and 1.0234 p.u., which now comply with the standards set by the IEEE. Besides, a comparison of the cost and GHG emission efficiency of the proposed hybrid system with existing (grid + DGs) and alternative (only DGs) scenarios was done. The findings showed that, among the scenarios examined, the proposed system is the most economical and produces the least amount of GHG emissions.

Survey Analysis of Potential Nuclear Safety Research of Thailand for International Research Collaborative Reinforcement in the 2020s

Abstract To achieve the long-term challenge of nuclear energy public acceptance in Thailand, nuclear safety research needed to be properly determined in both domestic and international directions, especially in the 2020s which was a period passing the Fukushima disaster over 10 years. Thailand Institute of Nuclear Technology (TINT) has studied nuclear safety research after the Fukushima accident to answer technical and social issues of nuclear power. An update of nuclear safety research from domestic experts and international surveys was needed in order to identify potential collaborative research to serve the goal of public acceptance reinforcement. The objective of this study was to survey, assess and rank the importance and knowledge level of nuclear safety research in Thailand among domestic experts in various fields. The survey was extended to collect the opinion of international participants of the ASEAN Network on Nuclear Power Safety Research (ASEAN NPSR) to analyze the similarity of the nuclear research interest for reinforcing the future collaborative project. As a result, the importance and knowledge level showed diverse important research topics with the priority of research scopes on human factor novel reactor technologies, and risk assessment. According to the ASEAN NPSR survey, the nuclear safety research of severe accidents, risk assessment, and novel reactor technologies were listed as potential collaborative projects. Also, the domestic and ASEAN NPSR survey results helped support the new collaborative research extension session in the annual ASEAN NPSR meeting to together discuss the potential nuclear safety research between members for the 2020s.

Include board members in peer groups, networking opportunities

While your nonprofit may frequently send senior staff and even the executive director to attend conferences, join peer groups and network with others in the field, it's not all that common for board members. And that's to their detriment, according to Eugene Fram, professor emeritus at Saunders College of Business at the Rochester Institute of Technology.

Resident Salary Compared to Living Wages at United States Training Institutions.

To compare living wages and salaries at US residency programs. It is unknown how resident salary compares to living wages across the United States (US). Cross-sectional analysis of publicly available resident salary affordability from training centers with post-graduate-year (PGY)-1 through PGY-7 resident compensation for 2022-2023 was compared with the Massachusetts Institute of Technology (MIT) Living-Wage Calculator. Resident salary to living wage ratios were calculated using PGY-4 salary for each family composition. Univariate and multivariable analysis of PGY-4 salary affordability was performed, accounting for proportion of expected living wages to taxes, transportation, housing, healthcare, childcare, and food, as well as unionization and state income-tax. 118 residency programs, representing over 60% of US trainees, were included, 20 (17%) of which were unionized. Single-parent families were unable to earn a living wage until PGY-7. Residents with 1 child in 2-adult (single-income) and 2-adult (dual-income) families earn below living wages until PGY-5 and PGY-3, respectively. Residents with more than 1 child never earn a living wage. Multivariable regression analysis using PGY-4 salary: living wage ratios in single-child, 2-parent homes showed food expense and unionization status were consistent predictors of affordability. Unionization was associated with lower affordability pre-stipend, almost equivalent affordability post-stipend, and lower affordability post-stipend and union dues. Resident salaries often preclude residents with children from earning a living wage. Unionization is not associated with increased resident affordability in this cross-sectional analysis. All annual reimbursement data should be centrally compiled, and additional stipends should be considered for residents with children.

IOT Based Light Automation System

Electronic &Telecommunication (E&TC) Department of JSPM’s Bhivrabai Sawant Institute of Technology & Research (BSIOTR) Wagholi, Pune. Light System involves controlling departmental lighting using the Internet of Things (IoT), allowing for a user-friendly automation system within the department. Instead of switching light manually ON or OFF, this system uses technology for doing it automatically. It enables automatic control of electronic appliances such as fans and lights. In this paper, we have implemented the operation of lights through the Blynk Application to control departmental light automation, allowing users to turn lights ON and OFF as needed. The system primarily utilizes the Raspberry Pi module, a crucial component of our smart light system implementation. It comprises both hardware and software components. The hardware includes Raspberry Pi 3b+ and a Relay Module, while the software utilizes the Python Language to issue commands for turning the lights ON and OFF. Raspberry Pi 3b+ module keeps all electrical Department appliances connected through a single interface for complete smart home system automation. With this setup, there is no need to use the conventional switches, and hence human effort required for the system is comparatively very less. Keywords: Department Light System , Internet of Things (IoT) , User-friendly automation, Raspberry Pi module, Relay Module, Blynk Application. .

Studies on Pearl Millet-Based Intercropping System under Rainfed Condition of Coimbatore District, Tamil Nadu, India

Aim: The aim of the study is to ascertain the response of pearl millet under intercropping system with pulses and their ability to produce higher yield under intercropping conditions. Study Design: The study was carried out in Randomized block design (RBD). Place and Duration of Study: The field experiment was conducted during rabi season of 2023-2024 at Karunya Institute of technology and Sciences, Coimbatore, Tamil Nadu. Methodology: The experiment was laid out in randomized block design and replicated thrice. It consisted of eleven treatments comprising of pearl millet as main crop and pulses viz., blackgram, greengram, redgram, cowpea and bengalgram as intercrops. Pulses were intercropped with pearl millet in replacement series of 4:1 and 6:1 row proportion. Results: Significantly higher plant height (186.03cm), dry matter accumulation (7386kg/ha), grain yield (2493 kg/ha) and B:C (2.50) ratio was recorded in pearl millet + blackgram (4:1). Further pearl millet equivalent yield (PMGEY) (2711.1 kg/ha) and Relative Crowding Coefficient (RCC) were higher in pearl millet with blackgram 4:1 ratio and Land Equivalent Ratio (LER) were higher in pearl millet + redgram at a ratio of 4:1. Conclusion: These results confirmed that, pearl millet + blackgram 4:1 intercropping system may be suggested to get greater net return and B: C ratio.

Peer groups, networking can aid board development

While it may be common for nonprofit executive directors and senior staff to attend conferences, join peer groups and network with others in the field, it's not all that common for board members. And that's to their detriment, according to Eugene Fram, professor emeritus at Saunders College of Business at the Rochester Institute of Technology.

Sexual violence amongst female undergraduate students in institution of higher learning in Enugu: Prevalence and awareness

Background: The rising cases of domestic violence has been a great concern to the general public. Objective: The prevalence and awareness of sexual violence on female undergraduates attending Institute of Management and Technology, Enugu was evaluated. Method: The study was a cross-sectional study that involved 400 female students, self-administered questionnaires was employed. Data was analysed using the Statistical Packages for Social Sciences (SPSS) version 23.0. Associations were tested using Chi square and p< 0.05, at 95% CI. Data was summarized as frequency distribution and chart. Result: Mean age of participants was 23.2 ±1.8. 354(88.5%) participants head about sexual violence prior to this study with one hundred and eighteen respondents (29.5%) being victims of sexual violence in one way or the other. 32.2% of them knew people who had suffered sexual violence. Commonest age of awareness was between 20-24 years(p=0.001). The source of sexual violence awareness was largely from friends (26%), face book (23.2%) and whatsap (20.3%) with least awareness from school teachers and newspaper (4.5%). Close relatives 52.6% were noted to be the commonest perpetrators of sexual violence, followed by family friends 31.6% and unknown persons 15.8%. Conclusion: There is high prevalence of sexual violence with little or no institutional based awareness program on sexual violence that is a threat to the general public.

Opening statement

Interested Australian universities with Interior Design/Interior Architecture degrees held an inaugural meeting in Sydney in 1996 to elicit interest in an association to advocate Interior Design/Interior Architecture education and research. In 1997 IDEA was formalised to encourage and support excellence in the discipline. This is the Inaugural publication of the annual ‘IDEA Referred Design Scheme’, one of the activities the IDEA committee promotes. Participating universities include: Curtin University of Technology, Queensland College of Art, Queensland University of Technology, Northern Territory University, Royal Melbourne Institute of Technology, Swinburne University of Technology, University of New South Wales, University of South Australia and the University of Technology Sydney.

Financial Services Authority Laws Against Non-Bank Financial Institutions Based on Outlaw Financial Technology

The jurisdiction of the Financial Services Authority to oversee non-bank financial institutions operating illegally on the basis of financial technology is outlined in Article 9 of Law No. 21 of 2011 concerning the Financial Services Authority. POJK No. 10/POJK.05/2022 regulates the legal proceedings initiated by the Financial Services Authority in response to violations committed by such illegal financial technology institutions. The objective of this research was to evaluate the current regulatory structure that oversees Non-Bank Financial Institutions (NBFIs) that engage in Online Financial Trading (OFT) and to pinpoint any regulatory shortcomings or challenges faced by financial authorities in their oversight of these companies. This study employs the Statutory Approach, the Case Approach, and the Analytical & Conceptual Approach to conduct normative research. Descriptive analytical methods were employed to acquire the data, and a qualitative approach was utilised to analyse both primary and secondary data. The research findings indicate that. The Financial Services Authority lacks the authority to regulate and enforce illicit fintech. The government established an Investment Alert Task Force (SWI) comprised of twelve ministries/institutions and financial services authorities, including those tasked with overseeing online loans and other illicit financial practices, in order to combat illegal fintech. OJK educates the public about the perils of illegal fintech and implements SWI in accordance with POJK Number 10/POJK.05/2022OJK so that it is possible to take decisive action against those who harm society through illegal fintech.

Studies on Nutrient Use Efficiency in Short Duration Red Gram (Cajanus cajan (l.) Millsp.) Varieties under Site-Specific Nutrient Management Techniques

Aim: To evaluate the nutrient use efficiency of short duration red gram varieties under site-specific nutrient management. Place and Duration of Study: The experiment was carried out in the rabi season of 2023 at an experimental farm in Karunya Institute of Technology and Sciences, Coimbatore. Experimental field was silty clay loam in texture with medium in available N (295 kg/ha), high in available P2O5 (kg /ha) and high in available K2O (285 kg/ha). Study Design: Split plot design. Methodology: The treatments consisted of three varieties in main plot namely V1- APK 1, V2- VBN 3, V3- VBN 1 and eight treatment in sub plots T1- (+NPK), T2 - N (-PK), T3 - P (-NK), T4 - K (-NP), T5 - PK (-N), T6 - NK (-P), T7 - NP (-K), and T8 - Control (-NPK). Result: Applying fertilizer as per recommended dose of nutrients without nutrient omission, resulted in increased nutrient use efficiency, agronomic efficiency, partial factor productivity and partial nutrient budget.

Desain Interaksi Website Edukasi Kekerasan Seksual di Era Digital Menggunakan Metode Design Sprint: Studi Kasus PPKS Institut Teknologi Telkom Purwokerto

The Telkom Purwokerto Institute of Technology is one of the Private Higher Education Institutions in Indonesia. The Telkom Purwokerto Institute of Technology has three faculties and fifteen study programs. To support all campus activities, this university has various types of facilities. One of the campus facilities is the availability of sexual violence handling services on campus. In the implementation of this service, there are still problems that occur, so a task force team named PPKS (Prevention and Handling of Sexual Violence) was formed. Over time, the current service system wants to be further developed into a better system in the future. During the research, problems were found, especially in terms of information delivery media. Based on these problems, the researcher wants to perform interaction design for the PPKS ITTP task force team website using the Design Sprint method. There are 5 stages that will be implemented. Namely Mapping, Sketching, Decide, Prototype, and Validate. This research will produce a final prototype (prototype of the result) that can be used for the development of the PPKS ITTP website. The results of the final prototype are Home-B (91.7%), Profile-B (90.8%), Module-B (91.7%), Quiz-B (92.7%) and Complaint-B (91.7%).

Use of waste plastic oil as a fuel in reactivity-controlled compression ignition engines: a bibliometric investigation from 2017–23

Abstract Waste plastic oil, generated through the pyrolysis of plastic without oxygen, known as plastic-to-fuel conversion, stands as a promising alternative fuel. This research employs bibliometric analysis, a quantitative method, to comprehensively assess publications in the domain of waste plastic oil integration within reactivity-controlled compression ignition engines. Utilizing Scopus as the primary repository post-2017, the study categorizes information into pivotal aspects, including influential journals, countries, authors, affiliations, document types, thematic areas, sponsors and keywords. The analysis reveals significant contributions from diverse nations, prominently India, China, Turkey and Malaysia. Noteworthy is the prevalence of Energy, Engineering and Chemical Engineering as thematic focal points, with the journal Fuel leading the count followed by the journal Energy emerging as a prominent conduit. Institutional contributions are prolific, led by Gandhi Institute of Technology and Management University and Vellore Institute of Technology. Renowned authors ‘Gugulothu S.K’ and ‘He Z’ play a pivotal role in shaping the discourse. The National Natural Science Foundation of China stands out as a primary patron. This bibliometric analysis provides a structured understanding of waste plastic oil integration in reactivity-controlled compression ignition engines, laying the groundwork for future research avenues. The study identifies potential research platforms beyond Scopus, including Web of Science, CrossRef, Science Direct and Google Scholar, as valuable repositories for further exploration. Moreover, after careful observation of the research articles published by the top 10 authors as found in the study, it was found that the authors share a few common characteristics that helped them in advancing the understanding and application of waste plastic oil in reactivity-controlled compression ignition engines. These are also summarized in the present study with supporting data.

A Protocol for Comprehensive Analysis of Gait in Individuals with Incomplete Spinal Cord Injury.

This is a protocol for comprehensive analysis of gait and affecting factors in individuals with incomplete paraplegia due to spinal cord injury (SCI). A SCI is a devastating event affecting both sensory and motor functions. Due to better care, the SCI population is changing, with a greater proportion retaining impaired ambulatory function. Optimizing ambulatory function after SCI remains challenging. To investigate factors influencing optimal ambulation, a multi-professional research project was grounded with expertise from clinical rehabilitation, neurophysiology, and biomechanical engineering from Karolinska Institutet, the Spinalis Unit at Aleris Rehab Station (Sweden's largest center for specialized neurorehabilitation), and the Promobilia MoveAbility Lab at KTH Royal Institute of Technology. Ambulatory adults with paraplegia will be consecutively invited to participate. Muscle strength, sensitivity, and spasticity will be assessed, and energy expenditure, 3D movements, and muscle function (EMG) during gait and submaximal contractions will be analyzed. Innovative computational modeling and data-driven analyses will be performed, including the identification of clusters of similar movement patterns among the heterogeneous population and analyses that study the link between complex sensorimotor function and movement performance. These results may help optimize ambulatory function for persons with SCI and decrease the risk of secondary conditions during gait with a life-long perspective.

Probing deformed nuclei: Experimental insights into excited states of 152,153,154Gd isotopes through fusion-evaporation reactions

The rare-earth region has been the focus of various studies aiming at the understanding of nuclear structure and providing information on the details of the reaction mechanism. The Gd isotopes belong to this group of nuclei and despite the available spectroscopic information, several open questions about their structure still exist, such as the inter-band transitions related to shape evolution or branching-ratios in deformed states. In addition, production cross sections of different reactions to Gd isotopes are largely unknown.In this work, we report on an experimental attempt to populate the excited states in the isotopes 152,153,154Gd by employing the heavy-ion fusion reaction 18O+138Ba → 156-xGd + xn in the 58-64 MeV energy range (center-of-mass). The experiment was conducted at the 9 MV FV Pelletron Tandem at the Horia Hulubei National Institute for Physics and Nuclear Engineering, employing the ROSPHERE array. Several branching-ratios for energy levels in 152,153Gd have been measured, offering new and updated values. Furthermore, relative cross sections regarding the fusion-evaporation reactions 138Ba(18O, 4n)152Gd, 138Ba(18O, 3n)153Gd, and 138Ba(18O, 2n)154Gd have been measured and compared with theoretical calculations with PACE4.

Celestial Mechanics Leading up to the AAS Division on Dynamical Astronomy

This talk reviewed key developments leading to the establishment of the AAS Division on Dynamical Astronomy. In the 1890s, Simon Newcomb calculated astronomical constants and ephemerides for solar system bodies that were internationally adopted and used for 80 yr. The introduction of punch card equipment in the 1940s and computers in the 50s allowed much faster computations. Launches of Sputnik, Explorer, Vanguard, and Mercury satellites led to computing the orbits of satellites around the Earth and the field of astrodynamics. Dirk Brouwer's death in 1966 resulted in the celestial mechanics faculty at Yale spreading across the country. The space program, radar observations, and faster computers propelled advances in celestial mechanics. Teams at the Jet Propulsion Laboratory and Massachusetts Institute of Technology developed solar system ephemerides using numerical integrations fit to optical observations and radar ranging measurements. It was time for the AAS Division on Dynamical Astronomy.

Assessing the Nutrient Balance and Nutrient use Efficiency of Various Concentration of Low-Density Polyethylene (LDPE) on Green Gram (Vigna radiata L. Wilczek) Cultivation

The pot experiment was to assessing the nutrient balance and nutrient efficiency of green gram crop under various levels of LDPE incubation conducted in Instructional farm (North), Karunya Institute of Technology and Sciences, Coimbatore. The experiment was laid out in Complete Randomized Design (CRD) with nine treatments and three replications. The treatment in the nutrient studies shows negative response in control and in 0.5% concentration of LDPE and has positive response in the remaining treatments, in agronomic efficiency the higher concentration has negative response and Apparent recovery studies shows that nitrogen recovery was high in higher concentration, phosphorous and potassium recovery has negative results in lower concentration.

Abstract PO2-19-10: CAPItello-292 Phase 3: An open-label, randomized study of capivasertib, fulvestrant, and investigator’s choice of CDK4/6 inhibitor (palbociclib or ribociclib) in HR+/HER2– advanced breast cancer

Abstract Background: Overcoming resistance to endocrine therapy in advanced breast cancer (ABC) is a major challenge, and there remains an unmet need for safe and efficacious treatment options. AKT pathway activation is implicated in resistance to endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) ABC. In the Phase 3 CAPItello-291 study, capivasertib (a potent inhibitor of all three AKT isoforms) plus fulvestrant significantly improved progression-free survival (PFS) versus fulvestrant in patients with aromatase inhibitor-resistant HR+/HER2– ABC. Simultaneous inhibition of the AKT and CDK4/6 pathways may delay CDK4/6 inhibitor resistance or re-sensitize tumors to endocrine therapy plus CDK4/6 inhibitors, leading to improved clinical outcomes. CAPItello-292 is an ongoing Phase 1b/3 study examining the efficacy and safety of adding capivasertib to fulvestrant plus a CDK4/6 inhibitor in HR+/HER2– ABC. Phase 1b has previously confirmed the recommended Phase 3 dose (RP3D) in combination with palbociclib to be tolerable with preliminary signals of clinical activity; determination of the RP3D in combination with ribociclib is currently being explored. Trial design: The Phase 3 component of CAPItello-292 is an open-label, randomized study assessing the efficacy of the addition of capivasertib to fulvestrant and the investigator’s choice of CDK4/6 inhibitors (either palbociclib or ribociclib) in patients with HR+/HER2− ABC following recurrence or progression on or within 12 months of the end of (neo)adjuvant endocrine therapy (HER2− defined as immunohistochemistry [IHC] 0, or 1-positive or IHC2-positive/in situ hybridization-negative). Approximately 628 patients will be randomized 1:1 to receive capivasertib (400 mg, oral twice daily, 4 days on and 3 days off) plus fulvestrant (500 mg intramuscularly every 28 days plus loading dose on cycle 1, day 15) and investigator’s choice of CDK4/6 inhibitor (125 mg palbociclib once daily for 21 days of each 28-day cycle or ribociclib at the determined RP3D) or fulvestrant plus investigator’s choice of CDK4/6 inhibitor alone. Patients will be treated until disease progression, unacceptable tolerability, or withdrawal of consent. Treatment beyond progression is permitted for patients with clinical benefit at the investigator’s discretion. The primary endpoint is PFS (by blinded independent central review [BICR]). The secondary endpoints include PFS in patients with AKT pathway-altered tumors, overall survival, time to second progression or death, objective response rate, duration of response, clinical benefit rate (all by BICR), physical functioning, global health status/quality of life and safety. The study plans to enroll patients from 23 countries and is planned to start at the end of 2023. Clinical trial identification: NCT04862663. Funding: CAPItello-292 is supported by AstraZeneca Editorial acknowledgment: AstraZeneca-funded medical writing support was provided by Suzanne Patel, Ph.D., from BOLDSCIENCE Inc. Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited). Citation Format: Hope Rugo, Barbara Pistilli, Julie Collins, Celina D’Cruz, Christopher Gresty, Roberto Sommavilla, Dhivya Sudhan, Claire Miller, Juyoung Ha, Patrick Neven. CAPItello-292 Phase 3: An open-label, randomized study of capivasertib, fulvestrant, and investigator’s choice of CDK4/6 inhibitor (palbociclib or ribociclib) in HR+/HER2– advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-10.

Abstract PS17-03: Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR positive/HER2-negative advanced breast cancer: exploratory analysis of PFS by AKT pathway gene from the Phase 3 CAPItello-291 trial

Abstract Background: In the Phase 3 randomized, double-blind CAPItello-291 trial, the addition of capivasertib (a potent, selective pan-AKT inhibitor) to fulvestrant in patients with aromatase inhibitor-resistant, hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (HER2− defined as immunohistochemistry [IHC] 0, or 1-positive or IHC2-positive/in situ hybridization-negative) advanced breast cancer (ABC) significantly improved progression-free survival (PFS) versus placebo + fulvestrant (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.51–0.71; p< 0.001). PFS benefit was observed in patients with detectable AKT pathway alterations (HR 0.50, 95% CI 0.38–0.65; p< 0.001) and without (0.70; 95% CI; 0.56–0.88). Here, we report PFS by gene within the AKT pathway-altered population. Methods: Patients were randomized 1:1 to receive fulvestrant (500 mg intramuscularly on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) with either placebo or capivasertib (400 mg twice daily; 4 days on, 3 days off). AKT pathway-alteration status (at least one qualifying alteration in the genes PIK3CA, AKT1, or PTEN) was determined post-randomization, using next-generation sequencing in tumor tissue. HRs were calculated using Cox proportional hazards models. Data cut-off Aug 15, 2022. Results: Of the 708 patients randomized to treatment, 289 (41%) had AKT pathway-altered tumors (capivasertib-fulvestrant n=155; placebo-fulvestrant n=134). In the AKT pathway-altered population, 43% had liver metastases and 40% primary endocrine therapy resistance. Prior therapy for advanced disease included: 89% of patients with ≥1 line of prior treatment, 71% with a prior cyclin-dependent kinase 4 and 6 inhibitor, and 18% with prior chemotherapy. Baseline characteristics were broadly balanced between treatment groups. Most patients with an AKT pathway-altered tumor had only one detectable alteration (272/289, 94%). Thirteen patients (capivasertib-fulvestrant n=4; placebo-fulvestrant n=9) had co-occurring PIK3CA and PTEN alterations, and four patients (capivasertib-fulvestrant n=2; placebo-fulvestrant n=2) had co-occurring PIK3CA and AKT1 alterations. Consistent PFS benefit of capivasertib-fulvestrant over placebo-fulvestrant was observed across all alterations (Table). The safety profile of capivasertib-fulvestrant in the AKT pathway-altered population was consistent with the overall population. Conclusions: Compared with fulvestrant alone, the addition of capivasertib to fulvestrant provided a consistent PFS benefit across alterations in all three key genes within the AKT pathway in patients with HR-positive/HER2-negative ABC. https://clinicaltrials.gov/: NCT04305496 Funding: CAPItello-291 is sponsored by AstraZeneca. Editorial acknowledgment: AstraZeneca-funded medical writing support was provided by Suzanne Patel, Ph.D., from BOLDSCIENCE Inc. Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited). Table. Citation Format: Sacha Howell, Hope Rugo, Mafalda Oliveira, Florence Dalenc, Javier Cortés, Henry Gómez, Xichun Hu, Komal Jhaveri, Petr Krivorotko, Sibylle Loibl, Serafin Morales Murillo, Meena Okera, Yeon Park, Joo Hyuk Sohn, Masakazu Toi, Eriko Tokunaga, Lyudmila Zhukova, Andrew Lloyd, Elza de Bruin, Coumaran Egile, Celina D’Cruz, Nicholas Turner. Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR positive/HER2-negative advanced breast cancer: exploratory analysis of PFS by AKT pathway gene from the Phase 3 CAPItello-291 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS17-03.