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  • Why Analysts Are Rethinking Hochschild Mining After Recent Forecast Shifts and Price Target Updates

    Why Analysts Are Rethinking Hochschild Mining After Recent Forecast Shifts and Price Target Updates

    Hochschild Mining’s stock narrative has shifted, as the Fair Value Estimate has been raised from £3.63 to £4.21 per share. This significant upward revision is driven by recent analyst activity. The change comes amid a modest drop in the Discount Rate and an improved outlook for revenue growth. Stay tuned to discover how investors can keep abreast of these evolving forecasts and what it means for the future of Hochschild Mining.

    Analyst sentiment on Hochschild Mining has been notably active, with significant price target revisions in recent months. Commentary from leading firms has highlighted both optimism and caution around the company’s valuation and outlook.

    🐂 Bullish Takeaways

    • Berenberg recently raised its price target on Hochschild Mining to 380 GBp from 280 GBp. This reflects renewed confidence in the company’s upside potential.

    • Canaccord continues to maintain a Buy rating on the shares with a new price target of 350 GBp, signaling belief in Hochschild’s underlying growth drivers and execution quality.

    • The upward adjustment in price targets underscores analysts’ recognition of revenue growth momentum and a positive shift in fundamentals.

    • Key drivers identified by analysts include improving cost control and stronger operational transparency.

    • Despite the bullish outlook, some reservations remain regarding valuation levels and the extent to which near-term upside is already priced into the stock.

    🐻 Bearish Takeaways

    • JPMorgan, represented by analyst Patrick Jones, lowered its price target to 370 GBp from 390 GBp. This reflects a more cautious stance even while maintaining an Overweight rating.

    • Berenberg has also demonstrated caution by previously lowering its price target from 300 GBp to 280 GBp, highlighting persistent concerns.

    • Bearish commentary centers on elevated valuation and the risks associated with near-term headwinds.

    • Some analysts caution that while operational improvements are evident, much of the positive outlook may now be reflected in the share price, limiting further short-term upside.

    Overall, while analysts acknowledge progress in Hochschild Mining’s growth and execution, opinions remain split. Ongoing valuation risks and priced-in optimism temper some of the renewed enthusiasm even as select firms raise their targets.

    Do your thoughts align with the Bull or Bear Analysts? Perhaps you think there’s more to the story. Head to the Simply Wall St Community to discover more perspectives or begin writing your own Narrative!

    LSE:HOC Community Fair Values as at Oct 2025

    • Hochschild Mining reported unaudited operating results for the first half of 2025, revealing a decline in silver production to 4,624 thousand ounces from 5,016 thousand ounces in the previous year. Gold production increased to 131.74 thousand ounces compared with 120.16 thousand ounces year-over-year.

    • The company’s total silver equivalent production rose to 15,559 thousand ounces, up from 14,989 thousand ounces in the same period last year. Total gold equivalent production also climbed to 187.45 thousand ounces from last year’s 180.59 thousand ounces.

    • Hochschild revised its 2025 Mara Rosa production target downward and now expects 35,000 to 45,000 ounces compared to the previous forecast of 94,000 to 104,000 ounces.

    • The company lowered its 2025 operations attributable production guidance, now projecting 291,000 to 319,000 gold equivalent ounces. This is a reduction from the earlier guidance of 350,000 to 378,000 ounces.

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  • Why export controls accelerate innovation: Evidence from the 2007 US ‘China Rule’

    Geopolitical rivalries have reshaped the global economy and have led to a resurgence of trade sanctions worldwide (Mohr and Trebesch 2025, Clayton et al. 2023, 2024). One common form of sanction is the export control, which restricts sales of certain items to specific destinations, usually geopolitical rivals. The stated purpose of export controls is to constrain the technological progress and military capacity of rivals. However, a key question surrounds such policies: do they inadvertently spur domestic innovation in rivals? In this column and a recent working paper, we bring granular firm-level evidence from China to this debate (Liu et al. 2025).

    We study the ‘China Military Catch-All Rule’, implemented in 2007 by the US Bureau of Industry and Security, which tightened export rules for certain dual-use items to China. When first proposed, the policy covered 77 HS six-digit categories; after an inter-agency review, 18 were removed. We exploit this change to estimate the policy’s causal effects on imports and innovation. Our baseline difference-in-differences strategy compares firms that imported controlled items before 2007 with firms that imported only the excluded items, which serve as our control group. We corroborate our results with propensity-score matching and synthetic difference-in-differences. To trace both trade and innovation responses, we link transaction-level Chinese customs data, firm surveys, value-added tax (VAT) invoice data on interfirm linkages within China, and the universe of Chinese patent applications.

    Large and persistent declines in controlled imports

    We find that the policy generated an immediate contraction in targeted trade (see Figure 1). Relative to control firms, pre-period importers of controlled goods were 18 percentage points less likely to import those goods from the US after 2007. The value of such imports fell by roughly 89% from the pre-period mean. Substitution from the rest of the world only partly offset the loss: the probability of importing controlled goods from any foreign source fell by about ten percentage points, and import value dropped by roughly 55%. Event-study estimates show a sharp break in 2007 that persists thereafter.

    Figure 1 Response of Chinese firm imports to export controls 

    Notes: The specification includes firm fixed effects, county-by-year fixed effects, and interactions of pre-period firm characteristics with year fixed effects. The pre-period characteristics include average pre-2007 firm sales growth, R&D spending, patent counts, and inventor counts. Standard errors are clustered at the firm level. The bars represent 95% confidence intervals. Source: Liu et al. (2025), Figure 2.

    Exposed firms responded with a broad surge in innovation

    Firms exposed to the export controls substantially increased innovation activity (see Figure 2). Compared to firms in the control group, they were 3.6 percentage points more likely to report any R&D spending, and their R&D outlays rose by about 49%. They were also 2.8 percentage points more likely to file any patent, with total applications up by about 41%. The innovation response was broad: patents related to controlled technologies rose by about 65%, while patents on other topics rose by about 42%. The number of active inventors at a firm increased by about 30%. These effects emerged quickly after 2007 and grew over time, indicating a persistent shift. The aggregate response is driven by non-state-owned firms.

    Figure 2 Response of Chinese firm innovation to export controls

    Notes: The specification includes firm fixed effects, county-by-year fixed effects, and interactions of pre-period firm characteristics with year fixed effects. The pre-period characteristics include average pre-2007 firm sales growth, R&D spending, patent counts, and inventor counts. Standard errors are clustered at the firm level. The bars represent 95% confidence intervals. Source: Liu et al. (2025), Figure 3 (a) and (b).

    Exposed upstream suppliers increased innovation in sanctioned domains

    We also examine upstream domestic suppliers, defined as firms that sold controlled products to treated firms before 2007. We identify suppliers of treated and control firms by leveraging firm-to-firm relationships from China’s VAT invoice database. Treated suppliers were 4.4 percentage points more likely to file any patent in controlled domains, and their related patent counts rose by roughly 360% relative to baseline. Patenting in other topics did not increase significantly. Thus, while directly exposed firms innovated broadly, upstream suppliers concentrated innovation specifically in the sanctioned technologies. These results highlight the importance of production-chain spillovers in the innovation response to export controls.

    Conclusion

    A growing literature studies how export controls matter for issuing countries. For example, Crosignani et al. (2024) show that US export controls hastened financial and real decoupling from Chinese firms: US suppliers saw lower stock returns, reduced bank lending, weaker profitability, and job losses. Other work shows how sanctions affect third countries. For example, US export controls on China prompted Japanese multinationals to exit the Chinese market; US Entity List sanctions on Huawei led Japanese suppliers to export less to China.

    By contrast, much less is known about how export controls affect the targeted economies. Recent work by Alfaro et al. (2025) finds that China’s 2010 rare-earth export quotas induced alternative supply and downstream innovation worldwide, while Egorov et al. (2025) document how post-2022 export sanctions disrupted production and supply chains in Russia, especially in strategic sectors. Our study complements this emerging literature by providing evidence on how a destination-specific export control can stimulate innovation within the targeted country itself.

    Overall, our results provide new empirical evidence on a key trade-off inherent to export controls as a geopolitical instrument. In the short run, they reduce the target’s access to critical inputs. Yet controls can also spur domestic innovation, and our results show that this response is economically meaningful in magnitude and persistence. As policymakers deploy export controls, they will need to weigh the short-run benefits against the long-run costs to ensure that the policies do not create the very problem they were intended to prevent.

    References

    Alfaro, L, H Fadinger, J Schymik and G Virananda (2025), “Trade and Industrial Policy in Supply Chains: Directed Technological Change in Rare Earths”, NBER Working Paper 33877.

    Clayton, C, M Maggiori and J Schreger (2023), “A Framework for Geoeconomics”, Working Paper.

    Clayton, C, M Maggiori and J Schreger (2024), “A Theory of Economic Coercion and Fragmentation”, Working Paper.

    Crosignani, M, L Han, M Macchiavelli and A F Silva (2024), “Geopolitical Risk and Decoupling: Evidence from US Export Controls”, Working Paper.

    Egorov, K, V Korovkin, A Makarin and D Nigmatulina (2025), “Trade Sanctions”, Available at SSRN 5404040.

    Fukao, K and I Deseatnicov (2025), “US export controls and the restructuring of global value chains: An analysis of Japanese multinationals’ exits from China”, VoxEU.org, 14 February.

    Hayakawa, K and K Ito (2025), “The ripple beyond borders: Indirect effects of US export controls on Japanese firms”, VoxEU.org, 1 August.

    Liu, X, Y Liu, A Makarin and J Wen (2025), “Export Controls and Innovation in Sanctioned Countries”, CEPR Discussion Paper 20690. https://cepr.org/publications/dp20690

    Mohr, C and C Trebesch (2025), “Geoeconomics”, Annual Review of Economics.

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  • SERENA-6 PROs: Switching to Camizestrant Improves QoL in HR+/HER2− Advanced Breast Cancer

    SERENA-6 PROs: Switching to Camizestrant Improves QoL in HR+/HER2− Advanced Breast Cancer

    Switching from aromatase inhibitor therapy to camizestrant combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) significantly delayed deterioration in global health status and pain among patients with hormone receptor–positive, human…

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  • Samsung Powers Three Days of Wellness, Running and Skateboarding in Paris With Wearable Technologies – Samsung Global Newsroom

    Samsung Powers Three Days of Wellness, Running and Skateboarding in Paris With Wearable Technologies – Samsung Global Newsroom

    From October 10 to 12, Paris came alive during the Vredestein 20km de Paris. Samsung hosted multiple pop-up experiences — including a Street League Skateboarding (SLS) competition and a Health…

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  • Addressing Drug Resistance in Lung Cancer

    Addressing Drug Resistance in Lung Cancer

    Drug resistance remains one of the greatest challenges in the treatment of advanced lung cancer, particularly in patients with tumors harboring monogenic alterations. Despite significant progress in targeted therapies, resistance ultimately limits the effectiveness of treatment, underscoring the need for new strategies to overcome both intrinsic and acquired resistance mechanisms.

    At the European Society for Medical Oncology 2025 Congress in Berlin, Germany, Pasi A. Jänne, MD, senior vice president for Translational Medicine and David M. Livingston, MD chair at Dana-Farber Cancer Institute, a professor of medicine at Harvard Medical School, discussed the underlying mechanisms of resistance, how to prevent resistance, and the role of antibody drug conjugates (ADCs) in overcoming barriers to optimal treatment response.

    Understanding the Origins of Resistance

    Resistance in lung cancer arises primarily through 2 mechanisms: pre-existing resistant clones and drug tolerance states. Pre-existing clones are subpopulations of tumor cells that harbor inherent resistance mechanisms before therapy begins. In contrast, the drug tolerance state emerges when tumor cells survive initial targeted therapy, entering a reversible, persistent state. These cells maintain some sensitivity to therapy but can eventually acquire multiple resistance mechanisms over time.

    Targeted therapy resistance is highly heterogeneous. In individual patients, multiple resistance pathways may develop simultaneously, including secondary mutations, bypass signaling pathways, and histologic transformation. For example, EGFR-mutant lung cancers can develop compound mutations, downstream pathway activation, or transform into small cell or squamous histology, each representing a distinct resistance mechanism. This complexity makes designing effective treatment strategies particularly challenging.

    “”Cancer is heterogeneous, and multiple resistance mechanisms can develop simultaneously,” explained Jänne, “which makes it challenging to determine the best therapeutic strategy.”

    Preventing Resistance Through Combination Therapies and Advanced Inhibitors

    One approach to managing resistance is the development of more potent inhibitors capable of overcoming resistance to earlier-generation drugs. For instance, osimertinib (Tagrisso; AstraZeneca) was designed to inhibit EGFR T790M mutations, while lorlatinib (Lorbrena; Pfizer Inc) targets resistance mutations arising after prior-generation ALK inhibitors.

    Combination therapy also plays a critical role. Clinical studies have shown that pairing targeted inhibitors with additional agents can improve response rates and delay the emergence of resistance. In EGFR-mutant lung cancer, trials combining osimertinib with MET inhibitors—such as capmatinib (Tabrecta; Novartis Pharmaceuticals Corporation) or savolitinib (Orpathys; HUTCHMED; AstraZeneca)—demonstrated higher response rates in patients with MET amplification or high MET expression. These biomarker-driven approaches illustrate the potential of combination strategies to preemptively circumvent specific resistance pathways.

    Targeting Drug-Tolerant, Persistent Cancer

    A challenging subset of lung cancer involves drug-tolerant, persistent tumor cells. These cells survive initial targeted therapy, often displaying stem cell-like properties, slow cycling, epithelial-mesenchymal transition (EMT) characteristics, and epigenetic modulation. Local therapies, such as consolidated radiation to residual lesions, have shown potential controlling these populations. Small studies demonstrate improved progression-free survival (PFS) and overall survival (OS) when radiation is combined with ongoing targeted therapy.

    “This drug-tolerant persistent state represents a therapeutic opportunity,” said Jänne. “If we can eliminate this intermediate population [cells that survive therapy but aren’t fully resistant], we may extend the benefit of first-line targeted therapy and delay resistance.”

    Preclinical models have further illustrated the potential of targeting this drug-tolerant state. In a mouse model of EGFR-mutant lung cancer, chimeric antigen receptor (CAR) T-cell therapy cured 4 out of 10 mice with durable responses, whereas treatment with osimertinib alone or with ADCs failed to produce long-term cures. These findings suggest that novel systemic therapies, including cellular therapies, may effectively eliminate residual resistant populations and extend the duration of benefit from first-line targeted therapy.

    Addressing Acquired Resistance

    Acquired resistance occurs when tumors initially respond to therapy but later progress. The pattern of progression—whether systemic or focal—guides subsequent treatment decisions. For localized progression, clinicians may employ targeted local therapies such as radiation, while continuing systemic targeted therapy. For systemic progression, tissue biopsies, often combined with liquid biopsies, provide critical insights into the mechanisms of resistance, which can then inform tailored treatment approaches.

    For example, EGFR-mutant tumors that acquire MET amplification can respond to combination therapy with osimertinib and MET inhibitors, showing response rates up to 58% compared with 34% for chemotherapy. Similarly, resistance mechanisms involving RET or ALK rearrangements can be addressed with combination strategies targeting the specific alterations. However, the heterogeneity of resistance mechanisms in individual tumors means that a single approach rarely addresses all pathways simultaneously.

    Small Cell Transformation and Novel Therapeutics

    Another mechanism of resistance in EGFR-mutant NSCLC is transformation into small cell lung cancer (SCLC). These transformed tumors are treated according to standard SCLC protocols, typically platinum-etoposide chemotherapy. Novel approaches, including tarlatamab (Imdelltra; Amgen) and ADCs, are being evaluated for efficacy in transformed SCLC. Early evidence suggests that combining targeted therapy with chemotherapy may enhance responses in this context, and ongoing trials will clarify the role of immune checkpoint inhibitors and ADCs in these transformed tumors.

    The Role of ADCs and Broader Therapeutic Approaches

    ADCs are emerging as a promising therapeutic option in resistant lung cancers, including those with EGFR mutations. ADCs can target a broad range of resistance mechanisms independent of the specific mutation, providing a more universal approach for patients lacking identifiable targetable alterations. For example, data from trials of troponin-2 ADCs and datopotamab deruxtecan-dlnk (Datroway;_Daiichi Sankyo, Inc) show response rates of approximately 40% in EGFR-mutant lung cancer, with some durable responses. These agents offer hope for patients whose tumors exhibit complex or polyclonal resistance mechanisms.

    The Need for Biomarkers

    Despite these advances, a major limitation in treating resistant lung cancers is the lack of predictive biomarkers. Biomarkers are essential for identifying which patients are most likely to benefit from combination therapy, local interventions, ADCs, or novel cellular approaches. Ongoing research aims to discover robust markers to guide treatment decisions and maximize therapeutic benefit while minimizing unnecessary toxicity.

    “Careful biomarker-driven strategies will be key to tailoring treatments and improving patient outcomes in resistant lung cancers,” Jänne said.

    Conclusion

    Drug resistance remains a formidable challenge in advanced lung cancer, but evolving strategies offer new hope. By understanding the origins of resistance—from pre-existing clones to drug-tolerant persistent states—clinicians can better tailor therapy to individual patients. Combination therapies, local interventions, ADCs, and CAR T cells all provide promising avenues to overcome resistance, while ongoing research into biomarkers will be crucial for guiding these approaches.

    REFERENCES
    Wolf J, Jänne P, Leighl N. Targeting oncogenes in NSCLC. Presented at: European Society for Medical Oncology 2025 Congress. October 17, 2025, to October 21, 2025. Berlin, Germany.

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  • New study sheds light on why GLP-1s could mitigate alcohol abuse

    New study sheds light on why GLP-1s could mitigate alcohol abuse

    Back in May, a study was published suggesting that popular weight-loss drugs such as Ozempic and Wegovy could curb alcohol cravings by as much as 70%. At the time, researchers weren’t entirely sure why the GLP-1s had such a profound effect on…

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  • Max Verstappen targets improved race trim for United States GP to fend off unknown pace of McLaren

    Max Verstappen targets improved race trim for United States GP to fend off unknown pace of McLaren

    Max Verstappen has targeted improvements for Sunday’s United States Grand Prix, to ward off the unknown of McLaren’s race pace, despite controlling Saturday’s Sprint as he claimed another victory.

    Verstappen closed to within 55 points of the…

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  • Perioperative Enfortumab Vedotin Plus Pembrolizumab May Represent New SOC in Cisplatin-Ineligible MIBC

    Perioperative Enfortumab Vedotin Plus Pembrolizumab May Represent New SOC in Cisplatin-Ineligible MIBC

    Perioperative enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) with radical cystectomy and standard pelvic lymph node dissection (RC + PLND) significantly improved event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR) rate vs RC + PLND followed by observation alone in patients with muscle-invasive bladder cancer (MIBC) who were not eligible for or refused cisplatin-based chemotherapy, according to data from the phase 3 KEYNOTE-905 study (NCT03924895).1

    The data, which were shared during the 2025 ESMO Congress as part of a late-breaking session, showed that enfortumab vedotin plus pembrolizumab (n = 170) led to a median EFS that was not reached (NR; 95% CI, 37.3-NR) vs 15.7 months (95% CI, 10.3-20.5) with the control (n = 174; HR, 0.40; 95% CI, 0.28-0.57; 1-sided P < .0001). The 12-month EFS rates in the respective arms were 77.8% and 55.1%; the 24-month rates were 74.7% and 39.4%.

    Top Takeaways from KEYNOTE-905:

    • Perioperative enfortumab vedotin plus pembrolizumab plus RC + PLND significantly improved EFS (HR, 0.40), OS (HR, 0.50), and pCR (57.1% vs 8.6%) vs RC + PLND alone in cisplatin-ineligible or -refusing patients with MIBC.
    • Consistent benefit with the addition of enfortumab vedotin plus pembrolizumab to RC + PLND was seen across subgroups: Improvements in EFS and OS were observed regardless of age, ECOG performance status, PD-L1 expression, or tumor stage, supporting broad applicability across patient subsets.
    • AEs were consistent with known toxicities of enfortumab vedotin and pembrolizumab, with no new safety signals identified.
    • The combination could represent a new standard of care in this high-need population.

    Moreover, the median OS with enfortumab vedotin plus pembrolizumab was also NR (95% CI, NR-NR) vs 41.7 months (95% CI, 31.8-NR) with the control (HR, 0.50; 95% CI, 0.33-0.74; 1-sided P = .0002). The 12- and 24-month OS rates in the enfortumab arm were 86.3% and 79.7%, respectively; in the control arm, these rates were 75.7% and 63.1%. The pCR rate with enfortumab plus pembrolizumab was 57.1% (95% CI, 49.3%-64.6%) vs 8.6% (95% CI, 4.9%-13.8%) with the control, translating to an estimated difference of 48.3% (95% CI, 39.5%-56.5%) between arms (1-sided P < .000001).

    “KEYNOTE-905 is the first phase 3 study to show improved efficacy outcomes with perioperative therapy relative to surgery for patients with MIBC who are ineligible for cisplatin-based chemotherapy,” Christof Vulsteke, MD, PhD, of the Integrated Cancer Center Ghent, AZ Maria Middelares, in Belgium, and the Center for Oncological Research at Antwerp University in Belgium, said in a presentation. “Perioperative enfortumab vedotin plus pembrolizumab added to RC + PLND may represent a new standard of care in this population with high unmet clinical need.”

    Topline data from KEYNOTE-905 were previously announced in August 2025.2

    What Did the KEYNOTE-905 Study Evaluate?

    The trial enrolled adult patients with MIBC who had an ECOG performance status ranging from 0 to 2, clinical stage T2 to T4aN0M0 or T1 to T4aN1M0 disease by central assessment, and at least 50% urothelial histology.1 Patients were either ineligible to receive cisplatin per Galsky criteria, or they had refused it.

    Patients (n = 344) were randomly assigned 1:1 to receive pembrolizumab at 200 mg every 3 weeks (Q3W) for 3 cycles with enfortumab vedotin at 1.25 mg/kg on days 1 and 8 Q3W, then RC + PLND followed by adjuvant pembrolizumab at 200 mg Q3W for 14 cycles plus enfortumab vedotin at 1.25 mg/kg on days 1 and 8 Q3W (n = 170) or RC + PLND followed by observation (n = 174). They were stratified based on cisplatin ineligibility (ineligible vs eligible but declining), clinical stage (T2N0 vs T3/T4aN0 vs T1 to 4aN1), and region (United States vs European Union vs most of world).

    The primary end point of the study was EFS by blinded independent central review, and key secondary end points were OS and pCR by central pathologist review. Investigators also evaluated safety and EFS by pCR status.

    In 2019, the study launched with 2 treatment arms, where patients were randomly assigned 1:1 to receive perioperative pembrolizumab with RC + PLND vs RC + PLND alone. A year later, in 2020, the third treatment arm, perioperative enfortumab vedotin plus pembrolizumab with RC + PLND, was added; patients were then randomly assigned 1:1:1 between the 3 arms. In 2022, investigators expanded the inclusion criteria to include patients who were eligible for cisplatin but refused cisplatin-based treatment. In the same year, they stopped randomly assigning patients to receive pembrolizumab plus RC + PLND and updated the trial enrollment to a 1:1 randomization for the enfortumab vedotin and control arms. They allowed patients in the control arm to receive adjuvant nivolumab (Opdivo) when indicated and available.

    The efficacy of enfortumab vedotin plus pembrolizumab and RC + PLND was compared with the control and evaluated in all concurrently randomly assigned patients; these patients comprised the intention-to-treat (ITT) population. Investigators evaluated safety in all patients who had received at least 1 dose of treatment, including surgery. KEYNOTE-905 will continue to examine additional hypotheses for the perioperative pembrolizumab arm, Vulsteke said.

    What Were the Baseline Characteristics of Patients Enrolled to KEYNOTE-905?

    The median patient age was 74.0 years (range, 47-87) in the enfortumab vedotin arm vs 72.5 years (range, 46-87) in the control arm. Most patients were male (80.6% vs 75.3%), had an ECOG performance status of 0 (60.0% vs 54.6%), and were from the European Union (45.9% vs 44.3%) or most of the world (41.8% vs 42.5%). The majority of patients were not eligible for cisplatin (83.5% vs 79.9%), although 16.5% vs 20.1% of patients were eligible but refused cisplatin-based treatment. In the enfortumab vedotin arm, 17.6% of patients had T2N0 (17.6%), T3/T4aN0 (78.2%), and T1 to 4aN1 (4.1%) disease; in the control arm, these rates were 18.4%, 75.9%, and 5.7%, respectively.

    What Additional Data From KEYNOTE-905 Are Important to Know?

    In the enfortumab vedotin arm, 167 patients started neoadjuvant treatment, and 144 patients completed it; 149 patients underwent surgery, and 147 patients had complete resection. Those who did not undergo surgery did not because of withdrawal from the trial (n = 10), toxicity (n = 7), disease progression (n = 3), or physician decision (n = 1). A total of 100 patients began the adjuvant phase. In the control arm, 156 patients underwent surgery, and 149 patients had complete resection. In the 18 patients who did not undergo surgery, reasons included withdrawal (n = 13), adverse effect (AE; n = 3), loss to follow-up (n = 1), and physician decision (n = 1).

    The median follow-up from randomization to the data cutoff date of June 6, 2025, was 25.6 months (range, 11.8-53.7).

    “PFS benefit was consistent across subgroups, including age, ECOG performance status, PD-L1 [expression,] and tumor stage,” Vulsteke said. “The OS benefit was [also] consistent across the subgroups, including age, ECOG performance status, and PD-L1 [expression].”

    An exploratory analysis of EFS by pCR status was conducted in the ITT population. In those who received enfortumab vedotin plus pembrolizumab and achieved a pCR (n = 97), the median EFS was NR (95% CI, NR-NR) vs 41.2 months (95% CI, 12.7-NR) in those in the control arm who achieved pCR (n = 15; HR, 0.43; 95% CI, 0.16-1.16). In those in the enfortumab vedotin arm who did not achieve a pCR (n = 73), the median EFS was 26.1 months (95% CI, 10.1-41.2) vs 14.2 months (95% CI, 10.1-19.5) for those in the control arm who did not have a pCR (n = 159; HR, 0.76; 95% CI, 0.51-1.14).

    “EFS benefits [were seen with] enfortumab vedotin plus pembrolizumab, irrespective of pCR,” he noted. “But when we look at the pCR, it’s a bad prognostic factor, but also the patients with a pCR in the control arm seem at risk and stay as a high unmet medical need.”

    What Was the Safety Profile of Enfortumab Vedotin Plus Pembrolizumab in KEYNOTE-905?

    Any-grade treatment-emergent AEs (TEAEs) occurred in all safety-evaluable patients in the enfortumab vedotin arm (n = 167) and 64.8% of those in the control arm (n = 159); these TEAEs were grade 3 or higher for 71.3% and 45.9% of patients, respectively. Serious TEAEs occurred in 58.1% of those in the enfortumab vedotin arm and 40.9% of those in the control arm. AEs led to surgery delay for 4.0% of patients in the enfortumab vedotin arm and 0.6% of those in the control arm. Toxicities led to dose reduction or discontinuation of enfortumab vedotin for 16.8% and 41.3% of patients; they led to discontinuation of pembrolizumab for 34.1% of patients; and they proved fatal for 7.8% of those in the enfortumab vedotin arm and 5.7% of those in the control arm.

    The most common TEAEs experienced in all phases of treatment with enfortumab vedotin plus pembrolizumab included pruritus (47.3%), alopecia (34.7%), diarrhea (34.1%), fatigue (32.3%), anemia (30.5%), decreased appetite (28.1%), dysgeusia (28.1%), constipation (27.5%), nausea (25.7%), rash (25.1%), increased aspartate aminotransferase level (24.0%), urinary tract infection (24.0%), weight decrease (19.8%), increased alanine aminotransferase level (19.2%), asthenia (17.4%), maculopapular rash (16.2%), and dry skin (15.0%). During the surgery phase, the most common TEAEs experienced in the enfortumab vedotin arm were anemia (13.7%), prostate cancer (11.6%), and urinary tract infection (8.9%).

    Enfortumab vedotin–related AEs of special interest included skin reactions (57.5%), peripheral neuropathy (36.5%), ocular disorders (17.4%), hyperglycemia (9.6%), and infusion-related reactions (1.2%). AEs of special interest associated with pembrolizumab included hypothyroidism (14.4%), severe skin reactions (13.8%), hyperthyroidism (4.8%), pneumonitis (3.6%), hepatitis (3.6%), thyroiditis (3.0%), colitis (2.4%), gastritis (2.4%), nephritis (2.4%), adrenal insufficiency (0.6%), myasthenic syndrome (0.6%), myocarditis (0.6%), and myositis (0.6%).

    “The safety profile of perioperative enfortumab vedotin plus pembrolizumab was manageable and consistent with prior reports of this regimen in the locally advanced or metastatic urothelial carcinoma setting,” Vulsteke concluded. “No new safety signals were observed.”

    Disclosures: Vulsteke disclosed receipt of research funding and medical writing support from Merck Sharp & Dohme LLC for the present work. He serves on the advisory board for MSD, Janssens-Cilag, GSK, Astellas Pharma, BMS, Leo Pharma, Bayer, AstraZeneca, Pfizer, Merck, and Atheneum Partners. Research grant to the institution was provided by MSD.

    References

    1. Vulsteke C, Kaimakliotis HZ, Danchaivijitr P, et al. Perioperative enfortumab vedotin plus pembrolizumab in participants with muscle-invasive bladder cancer who are cisplatin-ineligible: phase 3 KEYNOTE-905 study. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA2.
    2. Keytruda (pembrolizumab) plus Padcev (enfortumab vedotin-ejfv) significantly improved event-free and overall survival and pathologic complete response rate for certain patients with muscle-invasive bladder cancer when given before and after surgery. News release. Merck. August 12, 2025. Accessed October 18, 2025. https://www.merck.com/news/keytruda-pembrolizumab-plus-padcev-enfortumab-vedotin-ejfv-significantly-improved-event-free-and-overall-survival-and-pathologic-complete-response-rate-for-certain-patients-with-muscle/

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  • Arrow Electronics says that US trade curbs on its Chinese affiliates are being reversed

    Arrow Electronics says that US trade curbs on its Chinese affiliates are being reversed

    By Karen Freifeld

    (Reuters) -U.S.-based electronic components distributor Arrow Electronics said on Saturday the U.S. government was reversing trade restrictions placed on Arrow’s China-based affiliates for facilitating the sale of U.S. components found in weaponized drones used by Iran-backed groups like the Houthis.

    Arrow (China) Electronics Trading Co and another Arrow entity with six aliases in Hong Kong were added to the Commerce Department’s Entity List on October 8 in a Federal Register posting.

    Licenses are required to export goods and technology to companies on the list and are likely to be denied. Firms are placed on the list over U.S. national security or foreign policy interests.

    On October 8, Commerce said that drones operated by Iran-backed groups and their debris recovered in the Middle East since 2017 had U.S. components traced to sales tied to these Arrow-related entities.

    Arrow said on Saturday the Commerce Department told it the department would soon publish the reversal in the U.S. Federal Register and sent a letter Friday removing the restrictions in the meantime.

    “We have received official communication from the U.S. Commerce Department,” Arrow spokesman John Hourigan said in an email. “Arrow is authorized to resume shipping to and from these entities under the same conditions that applied prior to October 8.”

    Asked about the matter, a spokesperson for the U.S. Department of Commerce’s Bureau of Industry and Security said in an email: “BIS is committed to ensuring that export restrictions are appropriately targeted to protect national security.”

    Hourigan said the company operates in compliance with all laws and regulations. Centennial, Colorado-based Arrow Electronics had global 2024 sales of $28 billion.

    Hourigan said that Arrow Electronics (Hong Kong) Co. Ltd, which he described as a subsidiary when it was added to the Entity List, was not actually affiliated with Arrow Electronics.

    However, the six aliases tied to the Hong Kong company in the Federal Register posting are affiliated with Arrow and, the company said, would be removed from the Entity List.

    (Reporting by Karen Freifeld; Editing by Cynthia Osterman)

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    Within Mars’ Craters, Ice Deposits Have Recorded the History of the Planet

    On the surface of Mars, there are numerous features that tell of a past age when the planet was warmer and wetter, with rivers, lakes, and even an ocean that covered much of its northern hemisphere. These include river channels, delta…

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