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Medscape
2 hours ago
- Health
- Medscape
Targeted but Toxic? Addressing the Safety Challenges of ADCs
Antibody-drug conjugates (ADCs) are an evolving class of targeted cancer therapy that combines a monoclonal antibody with a cytotoxic payload or agent via chemical linkers. Attaching the monoclonal antibody with the cytotoxic agent enables an ADC to target cancer cells, maximizing efficacy and minimizing off-target toxicity. Several ADCs, including HER2+, HR+, and triple-negative breast cancer (TNBC) subtypes have shown significant efficacy in treating breast cancer. The ADCs currently approved by the FDA for the treatment of metastatic breast cancer and as an adjuvant treatment for HER2+ breast cancer include trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), patritumab-DXd, and sacituzumab govitecan (SG). Although ADCs have demonstrated significant efficacy, treatment-related toxicity, mainly from off-target effects of cytotoxic payloads and unintended bystander damage, remains a concern. A recent systemic review and meta-analysis by Zhu et al on ADCs found treatment-related adverse events of 91.2% for all-grade adverse events and 46.1% for grade ≥ 3 adverse events. Lymphopenia (53%) was the most common all ‐ grade adverse event, and neutropenia (31.2%) was the most common grade ≥ 3 adverse event. Approximately 13.2% of patients discontinued ADC treatment due to serious toxic events. This article discusses some of the common hematologic, cardiac, and gastrointestinal (GI) toxicities/adverse events associated with ADCs and their management. Managing Hematologic Adverse Events Neutropenia, anemia, and thrombocytopenia are common hematologic toxicities associated with ADCs. The most common cytopenia associated with T-DXd is neutropenia. In the DESTINY-Breast03 trial, any-grade neutropenia was observed in 42.8% of patients taking T-DXd. Although grade 3 or higher neutropenia was reported in 19.1% of patients, the DESTINY-Breast01 trial reported only 1.6% of patients experienced febrile neutropenia associated with T-DXd. The incidence of all-grade neutropenia associated with T-DM1 across trials ranges from 5% to 11% with grade ≥ 3 neutropenia, including febrile neutropenia, occurring in up to 6% of patients. Neutropenia-associated with ADC toxicity can be managed through dose modifications and temporary treatment holds. Prophylactic granulocyte colony-stimulating factor can decrease the incidence, duration, and severity of neutropenia and is indicated for patients with a history of neutropenic complications. Since the risk of developing febrile neutropenia with T-DXd is low (≤ 10%), prophylactic granulocyte colony-stimulating factor is typically not indicated. Regarding anemia, the EMILIA and TH3RESA trials reported the incidence of anemia associated with T-DM1 to be only 2.7%. However, findings from a randomized open-label phase 3 trial found grade 3 or higher anemia in 8.1% of patients receiving T-DXd. A phase 1/2 multicenter open-label study reported anemia in 18.7% of patients receiving patritumab-DXd, a HER3-directed ADC. A common approach to managing grades 3 and 4 anemia associated with ADCs involves withholding the treatment until anemia is lower than grade 2. The WSG-ADAPT, TH3RESA, and EMILIA trials found all-grade thrombocytopenia occurs in up to 28% of patients receiving T-DM1. The EMILIA trial reported severe thrombocytopenia in up to 12% of patients treated with T-DM1; the DESTINY-Breast03 trial reported grades 3 and 4 thrombocytopenia in 7% of patients receiving T-DXd; and a phase 2 study reported grades 3 or higher thrombocytopenia in 1.7% of patients receiving HER3-DXd. Managing thrombocytopenia involves reducing the dose of the ADC until patients recovery to grade 1 is achieved and continuing with the reduced dosage for the duration of treatment. Managing Cardiotoxicity Cardiotoxicity is a known adverse event of HER2-targeted therapies such as T-DM1 and T-DXd. HER2 receptors are usually expressed on cardiomyocytes and play a key role in normal fetal heart development and the growth and survival of adult cardiomyocytes. Preclinical studies suggest T-DM1 can exert more cardiotoxic effects than trastuzumab, though clinical evidence remains low. A pooled meta-analysis by Pondé et al of data from 1961 patients exposed to T-DM1 in seven trials found 3.37% experienced at least one cardiac event. Most of the events (2.04%) were grade 1 or 2 left ventricular ejection fraction (LVEF); grade 4 LVEF events were rare. Although no specific guidelines exist for the management of T-DM1-associated cardiotoxicity, general recommendations for ADC treatment from the 2022 European Society of Cardiology Cardio-Oncology guidelines suggest a baseline ECG prior to treatment initiation and then echocardiography every 3 months thereafter, along with natriuretic peptide monitoring throughout treatment. Treatment interruption and reassessment are indicated for patients whose LVEF drops to ≥ 10% from pretreatment value or to < 40%. For T-DXd, cardiac events were minimal in DESTINY-Breast01 and Breast03 trials, with few patients experiencing reversible LVEF reductions; no events of heart failure were reported. However, the DESTINY-Breast04 trial showed that 11.9% of patients receiving T-DXd who had not been previously treated with an anti-HER2 agent had LVEF reductions of 10%-19%, and 1.5% had > 20%. Management of ADC-related cardiac events includes reducing or permanently withdrawing treatment. Following treatment interruption, ADCs may be resumed with increased monitoring if cardiac function recovers. Permanent discontinuation may be required for patients whose LVEF remains significantly low or who develop heart failure. Managing Gastrointestinal Toxicity Nausea and vomiting are two of the most common GI toxicities associated with T-DXd treatment. In the DESTINY-Breast03 trial, 72.8% (187 of 257) and 6.6% (17 of 257) of patients had any grade and grade ≥ 3 nausea, respectively, post-T-DXd treatment. Vomiting was also commonly reported, with 44.0% (113 of 257) and 1.6% (4 of 257) of patients experiencing any grade and grade ≥ 3 vomiting, respectively. Based on these findings and other clinical trial data, the National Comprehensive Cancer Network Clinical Practice in Oncology guidelines reclassified T-DXd as highly emetogenic. The emetogenic classification of SG varies by guideline but is generally categorized as high-moderate or high. According to pooled analysis data by Pedersini et al, 65.6% and 43.7% of patients experienced nausea and vomiting, respectively, with SG therapy. Most cases of nausea and vomiting were grade 1 or 2, and approximately 10% were grade 3 or 4. T-DM1 is categorized as a low emetogenic since its associated toxicities are easier to manage. Prophylactic antiemetic therapy for nausea and vomiting associated with ADCs varies based on guidelines and emetogenic categorization. Due to their higher emetogenic risk, a 3- or 4-drug antiemetic regimen (eg, 5-hydroxytryptamine 3 receptor antagonist, dexamethasone, neurokinin-1 receptor antagonist, olanzapine) is recommended for T-DXd and SG. Due to its low emetic risk, prophylactic antiemetics are not usually recommended for T-DM1 but may be considered based on a patient's individual risk factors. In general, dose interruption or modification is recommended for patients on T-DXd or SG who experience grades 3 or 4 nausea and vomiting until they recover to grade 1 toxicity. Treatment with SG may be permanently stopped if grade 3 or 4 toxicity lasts for more than 3 weeks. Diarrhea is another common GI adverse event associated with ADC use and is reported to occur in 59.7% of patients treated with SG, 30.2% with T-DXd, and 17.5% with T-DM1. Management for ADC-associated diarrhea includes loperamide, intravenous fluids, metoclopramide with or without dexamethasone, and olanzapine for refractory cases. Preventive strategies include dietary modifications (eg, high fiber diet), oral supplements and probiotics, and nutritional counseling. Managing Interstitial Lung Disease Interstitial lung disease (ILD) is a group of lung disorders characterized by fibrosis or scarring of the lungs. Risk factors for the development of drug-induced ILD include increased age (≥ 60 years), smoking, pre-existing lung conditions, higher alcohol consumption, and renal failure. A pooled analysis of eight T-DXd monotherapy studies suggested 15.8% of the population developed ILD/pneumonitis with 77.7% experiencing grade 1 or 2 events. The DESTINY-Breast03 trial showed the incidence of drug-related ILD/pneumonitis with T-DXd to be lower at 10.5%. In phase 3 of the ASCENT trial, ILD associated with SG or T-DM1 was rare in patients with metastatic TNBC. In addition, the phase 1/2 study, U31402-A-J101, investigating HER3-DXd reported ILD in 6.6% of patients; most cases were grade 1 or 2, three were grade 3, and one was grade 5. Regular monitoring and assessment of patients are important to prevent ILD/pneumonitis. Per the current T-DXd ILD/pneumonitis guidelines, a computed tomography scan should be obtained prior to initiating ADC treatment and every 9-12 weeks thereafter during treatment. Patients who develop ILD/pneumonitis should undergo CT scans every 1-2 weeks (or as clinically indicated). In cases of suspected ILD/pneumonitis, consultation with a pulmonary specialist is recommended. Treatment for ILD/pneumonitis includes initiation of corticosteroid therapy immediately upon detection of grade ≥ 2 ILD/pneumonitis; corticosteroid treatment may be considered in patients with grade 1 ILD/pneumonitis. Guidelines for treating ILD/pneumonitis include starting corticosteroids immediately after detecting grade ≥ 2 ILD/pneumonitis and considering corticosteroid treatment in case of grade 1 cases. Future Directions Regular monitoring and prophylactic management are essential to reduce and mitigate ADC-related toxicities and maximize treatment benefits. Other toxicities associated with ADCs include neurological, embryo-fetal, ocular, and dermatological events. Continued research is needed to understand the mechanisms that contribute to ADC-related toxicities and provide additional management approaches to reduce risk. In addition, future research efforts should focus on the development of highly targeted therapeutics aimed at specific antigens, the creation of safer drug payloads, and the innovation of new linker technologies to reduce off-target effects. Novel ADCs are in development to enhance cancer immunotherapy by targeting immune cells or components of tumor microenvironment rather than tumor-associated antigens directly. These include immunostimulatory antibody conjugates that use immune-activating payloads (eg, Toll-like receptors 7 and 8, stimulators of interferon genes agonists) instead of traditional cytotoxins. Early clinical trials have evaluated immunostimulatory antibody conjugates against targets like HER2 and carcinoembryonic antigen. In addition, other ADCs are being developed to target elements of the tumor microenvironment such as T cells and fibroblasts. These novel approaches are likely to produce unique toxicity profiles, highlighting the need for a deeper understanding of their safety as development progresses.
The Star
9 hours ago
- Business
- The Star
All-in on AI increasingly a biz decision
Chinese companies are embracing artificial intelligence to speed up digital transformation and seek sustainable growth as the fast-evolving technology presents a significant opportunity for enterprises to boost operational efficiency and remain competitive, according to a new report released by global consultancy Accenture. The report said 46 percent of surveyed Chinese companies are using generative AI at scale, and embedding this cutting-edge technology into a slew of complex scenarios including research and development, design, manufacturing and supply chain management. The report found that Chinese companies have made great strides over the past year in strengthening their key digital capabilities, with 33 percent of interviewed firms recognizing that the integration of AI and cloud can drive product and service innovation. Moreover, 53 percent of Chinese companies are using AI to connect and integrate multiple business processes — 11 percentage points higher than the global average level. They are also investing in cloud and cybersecurity as 58 percent of polled enterprises said they are able to quickly update security strategies and tools. Although Chinese companies are accelerating the adoption of AI, only 9 percent are realizing significant improvements in terms of productivity, revenue and profitability from leveraging the technology, the report said. This is the eighth consecutive year that Accenture has traced the digital transformation journey of Chinese companies. The study surveyed more than 160 firms in seven sectors this year — high-tech manufacturing, automotive, engineering machinery, consumer goods, retail, chemicals and new energy. While Chinese companies are increasing investment in technological innovation to enhance their competitiveness amid uncertainties, they need to further harness the power of digital technologies to elevate operational efficiency and tackle challenges from growth pressure and global expansion, Accenture said. Samantha Zhu, chairperson of Accenture Greater China, said against the backdrop of accelerated changes in the global economic landscape, and mounting volatility and uncertainties, it is vital for Chinese companies to concentrate on innovation and speed up digital transformation, so as to achieve high-quality growth. "We can clearly see that leading companies have greater resilience in addressing various challenges, thus giving them an edge in adapting to the AI era. In the new wave of technological and business evolution, companies need to take holistic approaches to truly build strong resilience and capabilities, from organizational architecture and working models to governance," Zhu said. Yu Yi, technology lead at Accenture Greater China, said as innovation emerges as the main force driving business growth, the proportion of Chinese companies that step up investment and promote the application of AI across a wide range of sectors is rising dramatically. The report suggested that enterprises should systematically integrate AI into their commercial models, strategic decisions and business processes, while optimizing supply chains and utilizing AI to achieve real-time monitoring and rapid decision-making to optimize the allocation of resources. Pan Helin, a member of the Expert Committee for Information and Communication Economy, which is part of the Ministry of Industry and Information Technology, said the rapid adoption of digital technologies represented by AI will inject fresh impetus into the country's economic growth and speed up digital and intelligent upgrades in enterprises. Noting that some Chinese enterprises are facing mounting difficulties in the process of digital transformation — such as budgetary shortfalls and inadequate skills training — Pan said these companies should devise long-term plans for digital transformation and continuously pour money into this field. Li Haitao, dean of Cheung Kong Graduate School of Business in Beijing, said AI is profoundly reshaping the business landscape and is bound to transform various industries. Li said China boasts a large number of well-educated engineering talent and AI professionals, improved digital infrastructure such as 5G and computing networks, massive amounts of data and ever-increasing innovation capabilities, which provide a solid foundation for the training and adoption of AI models. - China Daily/ANN
South China Morning Post
a day ago
- Sport
- South China Morning Post
World Aquatics Championships: China's divers win 2 more golds as swimmers win a bronze
Chinese divers again won two golds in the water at the World Aquatics Championships in Singapore on Tuesday, while Tang Qianting failed to defend her 100m breaststroke crown. Advertisement The pick of diving action came in the men's 10m platform synchronised event, when China's Cheng Zilong and Zhu Zifeng stole first place, winning by just 0.93 points, as they claimed a total of 429.63. Neutral athletes Nikita Shleikher and Ruslan Ternovoi won silver with 428.70 points, while Americans Carson Tyler and Joshua Hedberg were third with 410.70 points. 'We believed in each other,' Cheng said. 'During our training, we didn't really have that many issues, so we just trusted each other. I trusted in Zhu [for the final two dives] and I trusted that we would be able to close it out.' Cheng and Zhu scored 60.18 for their third dive, the lowest points awarded in that round, but Shleikher and Ternovoi could put up only 76.68 in their final dive and had to watch as the Chinese pair hit 90.72 to reclaim the top spot. Chen Yiwen (left) and Chen Jia won the 3m synchronised springboard final with ease. Photo: Xinhua In the first diving final of the day, Chen Yiwen and Chen Jia dominated the women's three-metre springboard, scoring 325.20 for gold.
Borneo Post
2 days ago
- Entertainment
- Borneo Post
Beyond babysitting: How China's grandparents are reinventing retirement
Graduates perform during the graduation ceremony at Xinjiang Open University for Seniors in Urumqi, northwest China's Xinjiang Uygur Autonomous Region, June 27, 2025. (Xinhua/Wang Fei) BEIJING (July 29): With her silver hair neatly styled and a pearl necklace resting against a soft yellow blouse, Yin Song embodies the elegance of the pianist she's always been. But the large studio headphones over her ears and the video camera in front of her suggest something different. At 74, 'Grandma Piano,' as her online fans affectionately call her, now spends her time guiding audiences through the world of anime and video game music, sharing the same depth of feeling she once brought to Mozart and Chopin. A lifelong musician, Yin opened her social media account in 2022 to share her expertise. It wasn't until she analyzed the music from the hit game 'Black Myth: Wukong' that her channel suddenly took off. The 'grandinfluencer' now has more than 600,000 followers on the video-sharing platform Bilibili. For Yin, the experience has been unexpectedly transformative. 'We used to lead the young,' she said. 'Now they lead us, and I want to keep running alongside them,' embracing new ideas and ways of connecting. Yin's story reflects a subtle yet telling cultural shift. In a country where grandparents have long been expected to devote their retirement years to caring for grandchildren, an increasing number of older Chinese are quietly rewriting the script. They are embracing new roles as content creators, community volunteers, entrepreneurs, and part-time professionals. For many, retirement is no longer a retreat, but a second act. Yin is far from alone. By the end of 2024, over 30 million users aged 60 or above were logging in monthly on Xiaohongshu, one of China's most popular social media platforms. In just two years, the number of senior content creators has tripled, generating more than 100 million posts. These older digital pioneers are challenging long-held stereotypes from grandmothers redefining fashion, to retired professors distilling philosophy into viral short videos, and rural elders sharing their pastoral lives. Digital engagement is only part of the story. Many seniors are also returning to work, seeking purpose beyond their pensions. Zhu Honghua, 70, a former Beijing accountant enjoyed a comfortable monthly pension of around 8,500 yuan (about 1,191 U.S. dollars) and a leisurely life with her husband after retirement. But the routine began to wear thin. When a business contact invited Zhu back to accounting, she jumped at the chance. 'It's not just about the money,' she said. 'Having something meaningful to do every day is its own reward.' Zhu's case is hardly an outlier. A growing body of data suggests that many older Chinese are not only willing but eager to return to work. A 2023 survey by the China Association of Gerontology and Geriatrics found that 45 percent of those aged between 60 and 69 expressed a desire to remain in or reenter the workforce. Research from the Tianjin Academy of Social Sciences revealed similar patterns: 62.1 percent of people aged 60 to 65 said they wanted to keep working, while among those approaching retirement, aged 55 to 59, the figure was even higher, at 72.7 percent. While motivations vary, nearly half of those seeking post-retirement work cited a need for purpose, according to a 2022 report on senior reemployment. Others aimed to apply their skills or chase new ambitions. A third said they hoped to ease financial pressure or afford a better quality of life. The surge of interest in post-retirement work coincides with China's rapidly aging population. By the end of 2024, more than 310 million Chinese citizens were aged 60 or older, about 22 percent of the population. That share is expected to surpass 30 percent by 2035, when the number of seniors is projected to top 400 million. As waves of older workers reach retirement age over the coming years, policymakers and experts see both a warning and an opportunity. With educational attainment on the rise, China's older adults are seen not only as dependents, but as a vast reservoir of experience, skills and resources that could help offset the country's shrinking working-age population. China has taken steps to harness the power of its aging population. In its recent move, the government issued new guidelines this May, calling for more flexible and personalized job opportunities tailored to older adults, while pledging to dismantle outdated regulations that stand in their way. Local governments have moved quickly to implement the changes, building registries of senior talent, expanding employment services for retirees, and cultivating specialized human resource agencies to serve the growing 'silver economy.' Signs of change are beginning to emerge in the labor market. Retirees with backgrounds in engineering, medicine, education and skilled trades are returning as consultants, trainers or part-time specialists, lending decades of experience to fields in need. 'China has entered an aging society,' said Lu Jiehua, a sociology professor at Peking University. 'Tapping into older human resources isn't just about addressing demographic pressure. It's a crucial strategy for extending the country's demographic dividend.' – Xinhua China elderly music performance retirement
Borneo Post
3 days ago
- Business
- Borneo Post
Chinese startup brings cutting-edge AI glasses to the masses
Zhu Mingming, founder and CEO of Rokid, a Hangzhou-based technology company, poses for a photo at Rokid's flagship store in Yujiang District of Yingtan, east China's Jiangxi Province, July 10, 2025. (Xinhua/Liu Jinhai) NANCHANG (July 28): A decade after founding Rokid, entrepreneur Zhu Mingming turned heads at an economic forum in February with a simple remark: 'My speech is in my glasses, so I don't need a transcript.' Standing casually behind the podium in a hooded sweatshirt, Zhu confidently told the audience he was using a smart ring to flip through virtual slides on his AI glasses. Within hours, the clip went viral on Chinese social media, sparking a wave of inquiries from viewers eager to know where they could buy the product. Zhu, known as 'Misa' in tech circles, recently showcased the same model, Rokid Glasses, at an experience store in his hometown, Yujiang District of Yingtan City, in east China's Jiangxi Province, a region long regarded as a trade and production hub for eyewear. What made that February moment stand out wasn't just the technology; it was how seamlessly the glasses blended into everyday life. 'While I'm speaking here, I'm also checking my WeChat messages on a virtual screen right in front of my eyes, and you probably didn't even notice,' he said at the store. 'In the past, many people wanted smart glasses, but they were either too bulky, too clunky, or their AI capabilities were not strong enough, so in the end, they were little more than a Bluetooth headset,' Zhu said. Unlike those early models, the new-generation Rokid Glasses weigh just 49 grams, resemble regular eyewear, and offer robust battery life. Zhu credits much of this progress to rapid AI advancements in recent years. Zhu encouraged visitors at the store to try on the smart glasses. 'Give them a try, and you'll decide for yourself whether they could become an everyday device like smartphones in the future,' he said. 'A good product should first be a good pair of glasses,' Zhu added. 'Then a good headset, a good camera, and ultimately, a great AI device.' In addition to browsing social media and watching videos, the device can project real-time captions, translations, navigation prompts, and AI-generated answers directly onto the lens, powered by leading Chinese AI models such as DeepSeek and Doubao. With simple voice commands, users can ask for directions, identify objects, receive call notifications, or even solve math problems, without ever reaching for their phone. A staff member demonstrates a pair of smart glasses developed by Hangzhou-based technology company Rokid at Rokid's flagship store in Yujiang District of Yingtan, east China's Jiangxi Province, July 10, 2025. (Xinhua/Liu Jinhai) 'It's rare, even globally, for a company to develop such a highly integrated and fully functional product in such a lightweight form,' Zhu said. 'That's only possible because we've stayed committed to this path for the past 10 years.' Around 90 percent of Rokid's funding goes into research and development (R&D), which makes it a highly R&D-driven company even by global standards. 'Our booth is very popular in the Consumer Electronics Show in Las Vegas,' Zhu said. He noted that Rokid aims to make smart glasses an affordable everyday tech product. Priced at around 3,000 yuan, they are far more accessible than many international models that cost over 10,000 yuan. While similar products from other companies failed to win over consumers, Rokid is now facing the challenge of fulfilling orders on time, with over 300,000 units already sold. 'We didn't expect to be overwhelmed this quickly,' Zhu admitted. He is convinced that smart glasses are set to become the next transformative platform after smartphones. However, he acknowledges the industry is still in its early stages, with the main challenge being educating the market to attract more users. With a series of Rokid's innovative products in tow, Zhu is taking his next big step in his hometown. Yujiang is home to over 260 eyewear companies and ranks among China's top five optical manufacturing bases. But most of its industry remains focused on trade and conventional manufacturing. Rokid has signed a strategic agreement with the local government and plans to establish a production base, integrate the local supply chain, and forge cooperation with local colleges to train a new generation of technicians. 'The talent is already here,' Zhu said. 'People in Yujiang understand eyewear. Now we just need to help them understand smart glasses.' Zhu acknowledged the journey won't be quick, but he remains optimistic. 'If we can help transform the local traditional eyewear industry into a more innovative one, that would be the most rewarding outcome of all.' – Xinhua AI glasses artificial intelligence China technology
