A significant proportion of patients with cancer experience symptoms of sensory nerve damage from chemotherapy known as chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a major dose-limiting toxicity of many chemotherapeutic regimens. Early detection and quantification of CIPN is a significant challenge. It is hypothesized that the non-invasive, non-painful, Pressure-Specified Sensory Device (PSSD) will be a sensitive and specific tool for measuring CIPN. If CIPN can be detected early, then Oncology might be able to alter the drug regimen, and if CIPN persisted, then lower extremity nerve decompression would be possible. A prospective cohort of patients receiving chemotherapy were referred by their Oncologist. During the administration of their IV chemotherapy, the patient had PSSD testing of the index, little finger and finger and big toe pulp. Quality-of-life outcome instruments QLQ-CIPN20, and the Michigan Neuropathy Symptom Score Instrument were administered. Each patient was evaluated for the presence of a Tinel sign at known sites of nerve entrapment. Inclusion criteria were patients receiving neurotoxic chemotherapy (Vincristine, Taxol, or Cisplatin). Thirteen patients were enrolled. There were no complications from neurosensory testing. The PSSD was 80% sensitive and 100% specific identifying symptomatic neuropathy, p < .014, Chi Square and p < .05 using the Fisher exact test. PSSD testing became abnormal prior to the patient becoming symptomatic and prior to the presence of a positive Tinel sign. Non-invasive and non-painful neurosensory testing is feasible to do during chemotherapy IV infusion. This can identify changes in peripheral nerve function that correlate with a patient's symptoms and therefore can be used by the Oncologist to alter the patient's chemotherapy dosage, limiting chemotherapy toxicity, and make recommendations for surgical decompression if nerve compression persists.
With the rapid progress of molecular medicine, new target therapies for solid tumors have become available, leading to the creation of molecular tumor boards (MTBs) designated to evaluate potential individualized treatment options. Unlike other solid or liquid tumors, there is no standard and customized tool to analyze sarcoma. We analyzed the organization of MTB in referral centers for sarcomas treatment in Italy. A 30-question survey was designed in 2021 by the Regina Elena National Cancer Institute and distributed among Italian referral centers for pediatric and adult sarcomas. This survey was developed as part of Alliance Against Cancer (Alleanza Contro il Cancro, ACC) project to provide a descriptive analysis of the availability and organization of MTBs as well as the propensity to offer genomic profiling to sarcoma patients. A total of 6 out of 10 centers contacted answered the survey, and all stating centers declared to have an MTB. The composition of MTB was variable, with a dedicated oncologist in 83% of centers, although all cases discussed required the presence of the oncologist. 83% of centers met the ACC criteria for eligibility at MTB discussion. In 83% of cases both the primary and the metastases were analyzed, while in 17% only the metastasis were analyzed. The type of analysis available were target panel sequencing and whole exome sequencing (WES) in 100% of centers, whole genome sequencing (WGS) in 83%, RNA sequencing in 53%. Bioinformatics analysis software used were Illumina pipeline in 50% of centers; Ion Reporter (Thermo Fisher Scientific), QIAGEN CLC Genomics Variant Reporter and Archer Analysis in 33%, 17% and 33% of centers respectively. The knowledge base software for variant interpretation in precision oncology were Oncomine Reporter and Sophia, both in 17%. Other specific tools (e.g., CibersortX, GATK suite, and DEseq2) were used in 33% of centers. The time required for the analysis was ≤ 10 days in 33% of centers and > 10 days in 67%. In 83% of centers results are stored locally, and a database with clinical data and follow-up was recorded. MTBs were present in most sarcoma referral centers that answered the survey, albeit with different organizational arrangements. Although this survey should be regarded merely as a descriptive analysis of the early stages of MTB use in sarcomas, and is not representative of the national landscape as a whole, it highlights the clinical need to develop expertise in using MTB for rare cancers and to standardize the process and may serve as a basis for future larger-scale, prospective efforts aimed at harmonizing MTB practices across Italian sarcoma centers.
What is this summary about?This article presents a patient-friendly summary of the final results of the ENLIVEN phase 3 clinical study, which The Oncologist published in July 2025.The ENLIVEN study asked whether treatment with pexidartinib reduced the size of tenosynovial giant cell tumors (TGCT) and improved symptoms such as pain, stiffness, and physical ability to function in participants with TGCT.In 2019, the FDA approved pexidartinib in the United States for the treatment of symptomatic TGCT in patients who were not recommended to receive surgery due to the size, location, or likelihood of return of the TGCT. This approval came following the promising results of the ENLIVEN clinical study. In this article, we share the final results from the long-term study.What are the key takeaways?In patients with TGCT, pexidartinib demonstrated sustained improvements in pain, stiffness, and physical function; reductions in tumor size, which were maintained over time; and no new side effects.What were the main conclusions reported by the researchers?Pexidartinib continued to reduce the size of TGCT over time among participants. Pexidartinib was generally safe for use among the 91 participants included in the study. Researchers saw no new side effects in the extra 5.5 years of follow-up beyond those already reported in the clinical trial. The study offered valuable insight into the long-term benefits for patients with TGCT treated with pexidartinib.Clinical trial number: NCT02371369(www.clinicaltrials.gov).
Chemotherapy is an essential component of comprehensive cancer care and timely access can improve survival outcomes. The objective of this study was to assess the time to chemotherapy initiation and patient-reported barriers to cancer care among patients from Addis Ababa, Ethiopia. We conducted a retrospective study using a randomly selected sample of 350 patients with common cancers (breast [ICD-10: C50], cervical [C53], colorectal [C18-20], oesophageal [C15], gastric [C16] and ovarian [C56]) registered at the population-based Addis Ababa City Cancer Registry (AACCR) in 2021. Patients or their relatives were followed-up via questionnaire-based telephone interview and treatment data were extracted from their medical records. The time from pathological diagnosis to initiation of chemotherapy (time to treatment) was calculated. Regression analyses were conducted to identify predictors of chemotherapy initiation and treatment delays. Most patients (71.7%) received chemotherapy and the median time to treatment was 63 days (IQR 36.5 to 128 days). Patients reported considerable barriers to treatment regarding fear, cost and waiting times. Having health insurance (OR 2.70; 95% CI 1.33 to 5.50) and trust in healthcare professionals (OR 1.76; 95% CI 1.16 to 2.68) were associated with higher odds of receiving chemotherapy. Patients with cervical (OR 0.07; 95% CI 0.03 to 0.18), gastric (OR 0.21; 95% CI 0.05 to 0.86) or oesophageal cancer (OR 0.10; 95% CI 0.02 to 0.53) were less likely to initiate chemotherapy compared to breast cancer patients. Longer time to treatment was not associated with any of the assessed characteristics or perceived barriers. Over half of the cancer patients from Addis Ababa wait more than two months to initiate chemotherapy after a pathological diagnosis. Expanding oncology services and health insurance coverage could enhance access to treatment. Health professionals should promote patient trust by appropriately addressing their psychosocial needs, including cancer-related fear, to improve the uptake of treatment and thus clinical outcomes. Improving access to timely chemotherapy requires coordinated action across multiple levels. Strengthening health system capacity and care coordination is essential to reduce delays, while improving provider-patient communication and integrating psychosocial support can address fear and enhance treatment uptake and adherence. Expanding health insurance coverage may reduce financial barriers but must be accompanied by increased service availability to be effective.
Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Nevertheless, it is estimated that more than 5.7 million people globally are currently living with it. CRC development is influenced by various environmental factors, and the benefits of a healthy lifestyle, particularly dietary changes, are receiving growing attention. While the mechanisms linking specific nutrients to CRC carcinogenesis are still under investigation, evidence suggests that prognosis and long-term outcomes may be influenced by post-diagnosis dietary habits. Here we report data from the ECHO 2.0 study (Eating habits CHanges in Oncologic patients), an observational investigation focused on post-diagnosis dietary changes, among Italian CRC patients. Data were collected from 98 subjects through a questionnaire designed to investigate changes in their food consumption, supplement use, and adoption of specific diets following surgery. Ninety-eight patients (45 females and 53 males) completed the survey, with most aged 65 years or older. We observed that some patients reported positive dietary changes, including an increase in the consumption of vegetables, fresh fruit, and fish and shellfish, as well as a decrease in the intake of processed meat, desserts, red meat, animal fats, alcoholic beverages, refined bread and pasta, soft drinks, and baked goods. Despite CRC survivors made some positive changes to their nutritional habits, those modifications were mostly followed by a few of them, while over half of patients consumed nutritional supplements after diagnosis. Moreover, changes in nutritional habits were mainly adopted without consulting or informing the oncologist, and even if nearly half of patients believed that a moderate or strong link existed between cancer and nutrition, only one-third of them sought dietary information after being diagnosed. Our findings suggest that, after diagnosis, CRC patients have made modest dietary changes, with only a few increasing their consumption of healthy foods. Furthermore, a significant proportion of survivors did not seek dietary information after their diagnosis, highlighting a gap in patient empowerment. These results emphasize the important role of healthcare providers, particularly oncologists, in identifying diet as a potential risk factor and directing patients toward appropriate nutritional support.
Trastuzumab-based chemotherapy is the standard first-line treatment for patients with HER2-positive advanced or metastatic gastric cancer (GC). However, evidence on real-world outcomes according to the chemotherapy backbone remains limited. A total of 2,399 patients with GC treated with trastuzumab-based chemotherapy were analyzed, 486 patients were treated with trastuzumab/5-fluorouracil/cisplatin (HFP) and 1,913 patients were treated with trastuzumab/capecitabine/cisplatin (HXP). Time to subsequent treatment (TST) and overall survival (OS) were analyzed according to the type of chemotherapy backbone. With a median follow-up of 10.5 months, the median TST was 6.08 months [95% confidence interval (CI) 5.65-6.60] in the HFP group and 8.02 months (95% CI 7.72-8.57) in the HXP group (p < 0.0001). The median OS was 9.89 months (95% CI 8.94-10.87) for the HFP group and 13.27 months (95% CI 12.75-14.00) for the HXP group (p < 0.0001). Specifically, HXP followed by trastuzumab and capecitabine maintenance (HXP-HX) demonstrated the best outcomes with median TST of 13.44 months (95% CI 12.52-15.61) and median OS of 22.18 months (95% CI 20.83-24.44) compared with HXP followed by trastuzumab maintenance (HXP-H) and HXP alone (both p < 0.0001), which were also significant in multivariable analysis. HXP-HX showed the best survival outcomes for patients with locally advanced unresectable, or metastatic HER2-positive GC based on real-world big data analysis of the ToGA regimen, suggesting that HXP-HX is recommended over HXP-H. In the current immunotherapy era for HER2-positive GC, the potential role of capecitabine maintenance as part of combination strategies should be interpreted cautiously and warrants further investigation.
Cancer is a complex global health issue that continues to overburden healthcare systems worldwide. Estimates suggest that the burden of cancer will double in the next decade, further straining healthcare systems if effective interventions are not scaled up. One critical barrier to scaling up cancer interventions is the shortage of the cancer workforce, which is particularly severe in low- and middle-income countries (LMICs) in sub-Saharan Africa, many of which do not have a single oncologist. Task shifting offers a potential strategy to expand the cancer workforce. However, there is limited evidence on task shifting to advanced clinical professionals, such as pharmacists, who could help improve access to cancer control services. Pharmacists are integral members of the healthcare team and possess advanced clinical knowledge that can be leveraged to enhance cancer care. In many LMICs, pharmacists serve as the first point of contact for health complaints and minor ailments, positioning them to aid in early diagnosis and intervention for cancer.The objective of this study is to develop a conceptual framework, TASK PACT (Task Shifting Concepts for Pharmacists to Advance Cancer Control and Treatment), to systematically assess the feasibility of task shifting selected cancer control services to pharmacists. The framework was developed through an integrative review of the literature on task shifting, and is grounded in a synthesis of intellectual capital, organizational readiness for change, motivation, and change theories, and the theoretical domains framework. It provides a structured approach to explore the perspectives of pharmacists, oncologists, policymakers, and patients regarding the acceptability, readiness, and practical implementation of expanding pharmacists' roles in cancer control.The TASK PACT framework could serve as a practical tool for research that informs policy, guides implementation research, and supports the design of scalable, context-specific collaborative models of cancer care in sub-Saharan Africa. Its application could strengthen the oncology workforce, improve access to cancer control services, and generate evidence to inform broader health system strategies in LMICs.
Hand-foot syndrome (HFS) is a complication of many anticancer therapies and negatively affects patients' quality of life (QoL). Currently, little data are available on using non-pharmacological skin products as standard therapy for HFS. This study aims to investigate whether a specific set of cosmetic products is effective for managing HFS skin side effects in cancer patients. This single-arm study involved 53 cancer patients with grade 1 of HFS undergoing chemotherapy, targeted, or hormonal treatments at the European Institute of Oncology (IEO). The study included a baseline visit and a follow-up visit 45 days later. All enrolled patients were prescribed a set of four cosmetic products for skin treatment. Patients underwent instrumental measurement to evaluate skin hydration and erythema while their QoL was assessed using the Skindex-16 self-questionnaire. Additionally, physicians clinically evaluated the HFS severity, using the CTCAE (Common Terminology Criteria for Adverse Events) scale and by comparing patient photographs. No patients worsened. After 45 days, the application of the cosmetic set increases skin hydration by 33% (p < 0.0001), while skin erythema decreases by 82,9% (p < 0.0001). Patients also showed a significantly lower mean Skindex-16 score at 45 days (-35.5%, p < 0.0001) compared to baseline. These findings were associated with clinical improvement in HFS-related skin symptoms in 58.5% of patients. These results show that a set of cosmetic products specific for cancer skin care can effectively manage HFS-related symptoms, resulting in improved QoL for patients, regardless of the anticancer treatment received.
Combination therapies can be used to significantly improve clinical outcomes in patients undergoing treatment for cancer, however, they also present challenges when establishing the contribution of effect (COE) for each component. Although factorial trials remain the most rigorous approach for determining COE, they are often impractical, such as in settings with rare cancers, aggressive disease, evolving standards of care, or monotherapy components with limited activity. As more combination regimens are co-developed from the outset, alternative approaches to registrational trial designs are needed to balance scientific rigor with feasibility and patient acceptability. Thoughtfully designed alternative approaches can support an understanding of COE when grounded in prior evidence and mechanistic understanding. Four major categories of evidence emerge to support designing combination trials without factorial arms: (1) data from trials of the same combination in other tumor types; (2) data from trials of agents with similar mechanisms of action; (3) data from early-phase or parallel trials of the combination within the same disease setting; and (4) strong mechanistic or clinical evidence that a monotherapy component lacks activity and/or imposes harm, supporting omission of inactive arms. Early regulatory engagement, prespecified decision rules, and transparent justification of design choices are essential to ensure that combination regimens provide meaningful improvement in efficacy over monotherapies while minimizing unnecessary toxicity. Applying these principles to combination therapy development can maximize patient benefit while maintaining scientific rigor.
The clinical significance of endocrine therapy (ET) in patients with estrogen receptor-low (ER-low, 1-10%) breast cancer remains uncertain. Increasing evidence suggests that these tumors differ biologically from typical hormone receptor-positive cancers, raising questions about the true benefit of ET in this subgroup. This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to July 1, 2025. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for time-to-event outcomes were extracted directly or estimated from Kaplan-Meier curves when not explicitly reported. Pooled analyses were performed using random-effects models to account for between-study heterogeneity. The protocol was registered in PROSPERO (CRD420251055521). A total of six retrospective observational studies involving 8,765 patients with estrogen receptor-low breast cancer were included. Endocrine therapy was associated with improved overall survival (OS) (HR 0.81, 95% CI 0.69-0.95; p = 0.01; I2 = 0%) and disease-free survival (DFS) (HR 0.64, 95% CI 0.45-0.90; p = 0.01; I2 = 0%). Endocrine therapy was associated with improved overall survival and disease-free survival in patients with estrogen receptor-low breast cancer. These findings suggest that estrogen receptor-low breast cancer should not be uniformly considered endocrine-insensitive and that routine omission of endocrine therapy should be approached cautiously. Given that the available evidence is derived from retrospective observational studies, further prospective studies are needed to identify patients most likely to benefit from endocrine therapy.
Most research about the high costs of cancer care has focused on characterizing and mitigating the financial hardship patients and families experience after cancer-directed therapy. Few studies have examined how these costs prospectively influence treatment decision-making. Even fewer address how costs impact decisions about symptom-directed therapies. We aim to describe how patient-facing costs of care influence decisions about cancer-directed and symptom-directed therapies for advanced cancer. We analyzed semi-structured interviews with patients, care partners, clinicians, and health system leaders and clinical observations collected by investigators at 3 NCI-designated United States cancer centers between July 2019-May 2021. Two analysts conducted thematic analysis based on the Model of Financial Burden After Cancer Diagnosis. Analysis of 157 interviews and 92 observations identified 4 themes: (1) Insurance influenced treatment choice and location; (2) Medical costs influenced treatment choice, location, and timing; (3) Non-medical costs influenced treatment location and timing; and (4) Employment changes influenced treatment choice and timing. Patients and care partners emphasized costs of symptom-directed therapies; staff focused on costs of cancer-directed therapies. Patients and care partners described how employment influenced decisions about starting or continuing cancer-directed therapy, while staff noted how employment affected decisions about symptom-directed therapy. Patient-facing costs profoundly influence treatment decisions in advanced cancer care, but differences in perspective among patients, care partners, and clinicians can lead to oversights in treatment decision-making. Eliciting and incorporating patients' varied priorities into treatment decisions can minimize these oversights, better align treatment with goals of care, and reduce financial hardship.
Anaplastic thyroid cancer (ATC) is an extremely rare cancer with very poor prognosis. Targeted therapies have improved outcomes in selected patients, but molecular testing is often difficult because of the aggressive course, rapid clinical deterioration, and long turnaround times. This study aimed to provide real-world evidence on the management and outcomes of ATC and to evaluate the prognostic impact of molecular testing. This multicentric, retrospective study included patients diagnosed with ATC between 1992 and 2024 from the REGETNE-Thyroid Network. Factors associated with overall survival (OS) were analyzed using Cox proportional hazards models. 214 patients were included (median age 70.8 years; 56.5% female). Median OS was 4.5 months. Access to molecular testing (HR 0.42, p = 0.001) and BRAF V600E mutation (HR 0.50, p = 0.008) were associated with longer OS, whereas TERT promoter mutations were associated with shorter survival (HR 2.80, p = 0.014). Local surgery showed a favorable prognostic association, regardless of stage (IVa/IVb: HR 0.54, p = 0.026; IVc: HR 0.36, p < 0.001). In metastatic disease, immunotherapy (HR 0.31; p < 0.001), tyrosine kinase inhibitors (HR 0.40; p = 0.002) and their combination (HR 0.24; p = 0.001) significantly improved OS, whereas chemotherapy did not (HR 0.76; p = 0.096). Targeted therapy, used predominantly (>95%) in BRAF V600E-mutated ATC, was also associated with longer survival (HR 0.40; p = 0.001). Molecular testing was associated with improved survival in ATC, likely driven by the identification of actionable alterations with effective targeted therapies. Local management is key in all stages. Our findings also support immunotherapy, tyrosine kinase inhibitors and their combinations as key therapeutic options.
HIF-2α signaling is a central driver of clear cell renal cell carcinoma biology. With regulatory approval of the HIF-2α inhibitor, belzutifan, in the third- and fourth-line refractory setting, therapeutic targeting of this pathway has entered clinical practice. At the 2026 ASCO GU Cancer Symposium, two randomized phase III trials evaluated earlier integration of belzutifan: LITESPARK-022 (belzutifan plus pembrolizumab vs pembrolizumab alone in the adjuvant setting) and LITESPARK-011 (belzutifan plus lenvatinib vs cabozantinib in the post-PD-(L)1 setting). LITESPARK-022 demonstrated a disease-free survival benefit (HR 0.72; 95% CI, 0.59-0.87; P = .0003), with early and sustained curve separation, though grade ≥3 adverse events doubled and overall survival data remain immature. LITESPARK-011 enrolled patients after progression on prior PD-(L)1 therapy in the metastatic setting. The combination improved median progression-free survival (PFS; 14.8 vs 10.7 months; HR 0.70), objective response rate (ORR; 52.6% vs 40%), and duration of response (23 vs 12 months), with a manageable toxicity profile. Together, these studies suggest that earlier targeting of HIF-2α biology may improve disease control and durability. However, patient selection, toxicity considerations, and the absence of mature OS data remain critical factors in determining the optimal role of belzutifan-based strategies across disease states.
Patients with node-positive colon carcinoma commonly receive adjuvant chemotherapy, regardless the tumor's T-stage. However, early-stage tumors (pT1-2 CC) are largely underrepresented in landmark studies supporting this treatment. This study evaluates the application of adjuvant chemotherapy in those patients based on daily practice. Patients who underwent surgery for either pT1- or pT2-CC were identified from the nationwide SNAPSHOT database and stratified by age (<75 or ≥75 years). Competing risk regression and (cause-specific) Cox proportional hazard models identified factors associated with 5-year cumulative incidence of recurrence and overall survival (OS), respectively. Lymph node metastases were found in 381 out of 2,312 (16.5%) patients, of whom 275 (72.2%) received adjuvant chemotherapy. The cumulative incidence of recurrence was 0.09 (95% CI 0.06-0.12) and 0.18 (95% CI 0.11-0.27) in patients who did or did not receive adjuvant chemotherapy, respectively (P = .007). In patients under 75, adjuvant chemotherapy was associated with significantly higher OS (91.3% vs 68.1%, P < .001). Corresponding OS probabilities in elderly patients (≥75 years) were 84.5% vs 55.1%, P = .003. After adjusting for confounding, this difference remained only significant in patients under 75: HRadj 0.5, 95% CI 0.1-0.7 and HRadj 0.5, 95% CI 0.2-1.3, respectively. The recurrence rate was not significantly different between patients receiving capecitabine/oxaliplatin (CapOx) and those on Capecitabine monotherapy (CIF 0.09, 95% CI 0.06-0.14 vs 0.05, 95% CI 0.01-0.16, P = .49). Adjuvant chemotherapy is associated with reduced risk of recurrence in patients with node-positive pT1-2 CC. Advantages on OS could not be demonstrated in elderly pT1-2N1-2 patients.
Outcomes for patients with hormone receptor-positive, HER2-negative (HR+HER2-) advanced breast cancer have improved considerably in recent years and CDK4/6 inhibitors are the preferred first-line therapy for most patients. Newer therapeutic classes include PI3K/AKT inhibitors, oral selective estrogen receptor degraders (SERDs), proteolysis-targeting chimeras (PROTACs), poly ADP ribose polymerase (PARP) inhibitors, and antibody-drug conjugates (ADCs). The development and regulatory approval of these new therapies to treat HR+HER2- breast cancer raises the question of how to use and sequence this fast-growing armamentarium to maximize benefit for individual patients. Disease progression and resistance mechanisms emerging on treatment (therapeutic pressure) add further complexity by inducing molecular alterations; thus, a clear understanding of the mechanisms behind resistance to both endocrine and CDK4/6 inhibitor therapies and their implications for subsequent treatment is critical. In principle, the most effective and tolerable drugs should be used first with the goals of delaying chemotherapy and offering patients the best quality and duration of life. This review aims to explain the evolving treatment landscape for HR+HER2- advanced breast cancer and provides the scientific background for developing future treatment algorithms driven by preclinical and clinical results.
Jejunal carcinoma is an exceptionally rare malignancy with limited therapeutic options beyond chemotherapy. Polymerase epsilon (POLE) mutations in this tumor type is even rarer, yet it may represent a predictive biomarker for response to immune checkpoint inhibitors in jejunal cancer and agnostically. We report a 58-year-old male patient diagnosed with a POLE-mutated jejunal carcinoma. He presented with left-sided abdominal pain and was found to have an extremely large mass in the left upper quadrant. Biopsy confirmed jejunal adenocarcinoma. He was initially treated with two cycles of FOLFOX and, upon detection of the POLE mutation, nivolumab was added. After four cycles of chemo-immunotherapy, imaging demonstrated significant tumor regression. However, radiologic and clinical signs of subocclusion prompted treatment discontinuation and surgical resection. Histopathologic analysis revealed a complete pathological response, with no viable tumor cells. The patient is disease-free since January 2025. This case underscores the role of immunotherapy in POLE-mutated tumors regardless of the site of origin and highlights the potential usefulness of molecular profiling in rare malignancies. In line with the agnostic approach used for microsatellite instability, molecular-driven clinical trials should be prioritized over histology-based studies to optimize treatment strategies for these orphan diseases.
Globally, pancreatic cancer is one of the leading causes of cancer-related mortalities. Although FDA-approved chemotherapy regimens are available, rapid deterioration is often observed after first-line treatment. The PARP inhibitor niraparib may offer a therapeutic benefit in patients with advanced pancreatic cancer, necessitating thorough investigation. This was an open-label, single-arm, Phase II trial involving 37 patients with metastatic or unresectable pancreatic cancer with DNA damage repair (DDR) gene alteration. Patients were administered niraparib (either 300 or 200 mg daily, based on weight and platelet count) in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal. Efficacy was assessed using the 6-month progression-free survival rate as the primary endpoint. Of the 37 patients, 29 were evaluated for efficacy. The 6-month PFS rate was 41.38% (12/29 patients; 95% CI 4.70%- 100%), the median PFS was 4.4 months (95% CI 3.6-6.5 months), and the median OS was 10.3 months (95% CI 7.6 -15.9 months). Further subgroup analysis revealed that the BRCA1/2 germline mutation-positive patient group (n = 14) reported a 6-month PFS rate of 50% and a median overall survival (mOS) of 12.1 months, while the non-BRCA group (n = 15) showed a 6-month PFS rate of 33.33% and a median overall survival (mOS) of 10.3 months. Adverse events occurred in 78% of patients, the most common being anemia (27%), and no treatment-related deaths were observed. These data demonstrate clinical activity of niraparib in patients with metastatic or unresectable pancreatic cancers harboring DDR gene defects. Future studies are warranted to establish their roles in diverse genetic patient subpopulations. NCT03553004.
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line standard treatment for advanced lung adenocarcinoma with common EGFR sensitive mutations (exon 19 E746-A750 deletion and exon 21 L858R). However, the optimal management for rare or compound EGFR mutations remains undefined. We report a case of advanced lung adenocarcinoma with a rare compound EGFR L747S/L858R mutation. The patient underwent four lines of therapy, showing significant responses to alternating cycles of Osimertinib and Pembrolizumab-chemotherapy, despite intervening disease progression. The clinical course culminated in fatal treatment-induced myelosuppression, with an overall survival exceeding 43 months. This case underscores dynamic clonal evolution in advanced NSCLC: the initial L747S/L858R clone showed Osimertinib sensitivity, while subsequent resistance revealed a distinct profile (distinct TP53 mutation, MET amplification, high PD-L1/TMB) that explained the durable response to Pembrolizumab. These findings provide crucial evidence for sequential therapy strategies in compound EGFR mutations. Our findings also highlight the utility of Next Generation Sequencing (NGS) in identifying targetable resistance mechanisms, enabling prolonged survival in patients with compound EGFR mutations and offering valuable insights for clinical decision-making.
The seventh Kidney Cancer Research Summit was held as a hybrid virtual/in-person event in Boston, MA during July 17-18, 2025. This conference, which aims to help guide the design of kidney cancer clinical trials and research, centers around projects that showcase the most impactful basic, translational, and clinical data evolving in renal cell carcinoma (RCC), and brings together clinical oncologists, physician scientists, translational researchers, and patient advocates. The abstract presentations were published as a supplement in The Oncologist (https://academic.oup.com/oncolo/issue/30/Supplement_2). This perspective will provide the layout of the current RCC research landscape as discussed and debated among the stakeholders at the conference as well as more recent updates.
Pancreatic ductal adenocarcinoma (PDAC) remains largely resistant to immunotherapy, with response rates below 5%. Emerging evidence suggests that immune exclusion in PDAC is actively maintained by oncogenic KRAS signaling. Mechanistic studies implicate three coordinated processes: autophagy-mediated degradation of MHC-I and impaired antigen presentation, expansion of suppressive myeloid populations, and desmoplastic stromal remodeling that restricts cytotoxic T-cell access to malignant epithelium. These barriers are at least partially reversible. Inhibition of autophagy restores surface MHC-I expression and re-enables antigen-dependent CD8+ T-cell killing. Suppression of KRAS pathway signaling remodels the myeloid compartment, alters stromal architecture, and increases intratumoral CD8+ T-cell infiltration in experimental systems. Recent studies further demonstrate that combining allele-specific KRAS inhibition with multi-arm immunotherapy can produce durable responses in resistant PDAC models. Spatial profiling data also suggest that immune architecture differs by KRAS allele, with KRAS G12D tumors more frequently exhibiting stromal T-cell segregation and KRAS G12R tumors demonstrating altered immune proximity and metabolic dependence. Together, these findings support a model in which KRAS-targeted therapy functions not only as tumoricidal therapy but also as immune conditioning of the tumor microenvironment. Translating this biologic reversibility into durable clinical benefit will require rational, barrier-specific, and allele-informed combination strategies.