Therapy For Advanced Cancer Research Articles

Advancements in Cancer Therapy: Mycoviruses and Their Oncolytic Potential

Advancements in Cancer Therapy: Mycoviruses and Their Oncolytic Potential

Vaccination Against Androgen Receptor Splice Variants to Immunologically Target Prostate Cancer

Background/Objectives: Androgen receptor (AR) expression and signaling are critical for the progression of prostate cancer and have been the therapeutic focus of prostate cancer for over 50 years. While a variety of agents have been developed to target this axis, many of these fail due to the emergent expression of AR RNA splice variants, such as AR-V7, that can signal independently of ligand binding. Other therapies, such as vaccination against prostate-specific antigens, have achieved FDA approvals but have fallen short of being incorporated as standard-of-care therapies for advanced prostate cancer. This may be due to the elevated level of immunosuppression observed in prostate cancer, which remains largely refractory to immune checkpoint blockade. Methods: We developed a vaccine targeting AR-V7, a common isoform associated with treatment resistance, and demonstrated its ability to elicit AR-V7-specific immunity and enable anti-tumor responses against AR-V7+ cancers in subcutaneous tumor models. Results: Our studies also revealed that AR-V7 expression conferred an immune suppressive phenotype that was significant in a non-AR-dependent prostate cancer model. Notably, in this model, we found that vaccination in combination with enzalutamide, an AR antagonist, suppressed these aggressive immune suppressive cancers and resulted in enhanced survival in comparison to control vaccinated and enzalutamide-treated mice. While anti-PD-1 immune checkpoint inhibition (ICI) alone slowed tumor growth, the majority of vaccinated mice that received anti-PD-1 therapy showed complete tumor elimination. Conclusions: Collectively, these results validate the importance of AR signaling in prostate cancer immune suppression and suggest the potential of AR-V7-specific vaccines as therapeutic strategies against prostate cancer, offering significant protective and therapeutic anti-tumor responses, even in the presence of androgen signaling inhibitors.

INNV-06. ADULT GLIOBLASTOMA WITH MISMATCH REPAIR DEFICIENCY FORMS A DISTINCT HIGH-RISK MOLECULAR SUBGROUP FOR WHICH TREATMENT WITH IPILIMUMAB-NIVOLUMAB SHOWS SURVIVAL ADVANTAGE

Abstract Glioblastoma is the most frequent and malignant primary brain tumor. Although the survival is generally dismal for glioblastoma patients, risk stratification and the identification of high-risk subgroups is important for prompt and aggressive management. The G1-G7 molecular subgroup classification based on the MAPK pathway activation has offered for the first time a non-redundant, all-inclusive classification of adult glioblastoma. Five patients from the large, 220-patient prospective cohort showed germline mutations in mismatch repair (MMR) genes and significantly worse median survival (3.25 months post-surgery) than those from other subgroups or from the rest of the cohort adjusted for age. These tumors were assigned to a new subgroup, G3/MMR, a spin-off from the major G3/NF1 subgroup, as they generally show genomic alterations leading to RAS activation. An integrated clinical, histological, immunohistochemical and molecular analysis of the G3/MMR tumors showed distinct characteristics as compared to other glioblastomas, including those with iatrogenic high tumor mutation burden (TMB), warranting a separate subgroup. Among these, prior history of cancer, midline location or multifocality, presence of multinucleated giant cells, positive p53 and MMR immunohistochemistry, and specific molecular characteristics, including high TMB, alert to this high-risk G3/MMR subgroup. High TMB constitutes the criterium for treatment with immune checkpoint inhibitors in solid cancers. The FDA-approved first-line therapy for advanced non-small cell lung cancer and high-TMB colorectal cancer is with the dual ipilimumab-nivolumab regimen. One of the five G3/MMR subgroup patients received the dual ipilimumab-nivolumab regimen and survived much longer than the rest of the G3/MMR patients, setting a proof-of-principle example for the treatment of these very aggressive G3/MMR glioblastomas.

Short-term outcomes of a phase II trial of perioperative capecitabine plus oxaliplatin therapy for advanced gastric cancer with extensive lymph node metastases (OGSG1701)

Short-term outcomes of a phase II trial of perioperative capecitabine plus oxaliplatin therapy for advanced gastric cancer with extensive lymph node metastases (OGSG1701)

Unveiling the influence of tumor and immune signatures on immune checkpoint therapy in advanced lung cancer.

This study investigates the variability among patients with non-small cell lung cancer (NSCLC) in their responses to immune checkpoint inhibitors (ICIs). Recognizing that patients with advanced-stage NSCLC rarely qualify for surgical interventions, it becomes crucial to identify biomarkers that influence responses to ICI therapy. We conducted an analysis of single-cell transcriptomes from 33 lung cancer biopsy samples, with a particular focus on 14 core samples taken before the initiation of palliative ICI treatment. Our objective was to link tumor and immune cell profiles with patient responses to ICI. We discovered that ICI non-responders exhibited a higher presence of CD4+ regulatory T cells, resident memory T cells, and TH17 cells. This contrasts with the diverse activated CD8+ T cells found in responders. Furthermore, tumor cells in non-responders frequently showed heightened transcriptional activity in the NF-kB and STAT3 pathways, suggesting a potential inherent resistance to ICI therapy. Through the integration of immune cell profiles and tumor molecular signatures, we achieved an discriminative power (area under the curve [AUC]) exceeding 95% in identifying patient responses to ICI treatment. These results underscore the crucial importance of the interplay between tumor and immune microenvironment, including within metastatic sites, in affecting the effectiveness of ICIs in NSCLC.

Unveiling the influence of tumor and immune signatures on immune checkpoint therapy in advanced lung cancer

This study investigates the variability among patients with non-small cell lung cancer (NSCLC) in their responses to immune checkpoint inhibitors (ICIs). Recognizing that patients with advanced-stage NSCLC rarely qualify for surgical interventions, it becomes crucial to identify biomarkers that influence responses to ICI therapy. We conducted an analysis of single-cell transcriptomes from 33 lung cancer biopsy samples, with a particular focus on 14 core samples taken before the initiation of palliative ICI treatment. Our objective was to link tumor and immune cell profiles with patient responses to ICI. We discovered that ICI non-responders exhibited a higher presence of CD4+ regulatory T cells, resident memory T cells, and TH17 cells. This contrasts with the diverse activated CD8+ T cells found in responders. Furthermore, tumor cells in non-responders frequently showed heightened transcriptional activity in the NF-kB and STAT3 pathways, suggesting a potential inherent resistance to ICI therapy. Through the integration of immune cell profiles and tumor molecular signatures, we achieved an discriminative power (area under the curve [AUC]) exceeding 95% in identifying patient responses to ICI treatment. These results underscore the crucial importance of the interplay between tumor and immune microenvironment, including within metastatic sites, in affecting the effectiveness of ICIs in NSCLC.

Plain language review: the safety of relugolix combination therapy for advanced prostate cancer.

Advanced prostate cancer is a cancer that began in the prostate (a part of the male body) and has spread to other parts of the body. This is a review of two clinical research studies of patients with advanced prostate cancer who were treated with relugolix combination therapy. Relugolix is a medicine taken by mouth that lowers a male sex hormone, called testosterone. Relugolix is sometimes combined with other medicines such as novel hormonal therapies (NHTs) or chemotherapy to treat advanced prostate cancer. In one study, patients were treated with relugolix combined with an NHT (abiraterone or apalutamide). In a second study, patients were treated with relugolix combined with an NHT (enzalutamide) or chemotherapy (docetaxel). Researchers wanted to understand what possible side effects may happen due to taking these medicines together as prescribed. They also wanted to see if relugolix combination therapy worked to lower testosterone in the same way as relugolix taken alone. Researchers found that most of the side effects of relugolix combined with an NHT or chemotherapy were mild or moderate. Side effects of relugolix combination therapy were similar to the side effects of the medicines when taken alone. However, patients who received relugolix with enzalutamide or docetaxel were more likely to have a serious side effect compared with patients who received relugolix taken alone. Testosterone stayed below 50 nanograms per deciliter (known as castration levels) for patients who received relugolix with NHT or chemotherapy. Patients who receive relugolix combination therapy generally experience mild or moderate side effects, rather than serious side effects. No new safety issues were found during these studies. Patients maintained low testosterone levels. Patients and their doctors should discuss the benefits and possible harms of relugolix combination therapy to treat advanced prostate cancer.

“Repotrectinib: a promising new therapy for advanced non-small cell lung cancer”

Non-small cell lung cancer (NSCLC) is the major cause of cancer-related mortality worldwide, accounting for 84% of lung cancer cases. The newly FDA-approved kinase inhibitor, Repotrectinib (AUGTYRO), offers a promising option for treating advanced or metastatic NTRK/ROS1-positive NSCLC. Repotrectinib has demonstrated significant efficacy in clinical trials. Notably, the phase 1/2 TRIDENT-1 study showed impressive progression-free survival and intracranial activity in both TKI-naïve and pre-treated patients. With its high response rates and manageable side effects, Repotrectinib is set to play a significant role in treating ROS1+and NTRK+advanced solid tumors, highlighting the ongoing need for research and clinical application.

Development of a Leg And Walking Self-exercise (LAWS) program for older adults during cancer treatment.

We developed a self-directed Leg And Walking Self-exercise (LAWS) program informed by the Exercise is Medicine initiative and evaluated the feasibility and acceptability of this program in older adults with cancer. Over a 1-year period, we prospectively enrolled 40 older adults who received a comprehensive geriatric assessment (CGA) at a geriatric oncology service and initiated a new line of systemic therapy for advanced cancer as inpatients. LAWS is a tailored, self-directed exercise program consisting of leg resistance training and walking. Exercise adherence was recorded using an exercise diary to assess feasibility. Patient perspectives on this program were evaluated using the Feasibility of Intervention Measure (FIM) and Acceptability of Intervention Measure (AIM), with a score range of 1-5, higher being better. Overall, 28% of patients were fit, 53% pre-frail, and 20% frail based on the CGA. During hospitalization (average 12days), 63% of the patients adhered to exercises at lowest intensity during more than 50% of their inpatient stay: on average, 2.8 leg exercises, 23 repetitions a day, 5.6days/week, and 19min of walking a day, 4.9days/week. Patients rated their perceived exertion at 3.0 for leg exercise and 3.0 for walking on a 1-10 Likert scale. During the period between discharge and their first outpatient appointment (average 11days), 71% of patients adhered to the LAWS program. Mean scores of FIM and AIM were 4.2 (SD = 0.5) and 4.2 (SD = 0.7), respectively. For older adults undergoing cancer treatment, LAWS is a feasible and acceptable self-directed exercise program.

Renewed Insight into Cancer Mechanism and Therapy: Advances, Challenges, and Future Directions

Cancer remains a complex and multifactorial disease characterized by genetic mutations, epigenetic changes, and alterations in cellular signaling pathways. While traditional treatments such as surgery, chemotherapy, and radiation have been the backbone of cancer therapy, their limitations, including drug resistance, recurrence, and significant side effects, have driven the search for more targeted and personalized treatment approaches. This review provides an in-depth exploration of recent advances in cancer research and therapy, focusing on molecular mechanisms, genetic alterations, and the tumor microenvironment, all of which play pivotal roles in tumor initiation and progression. Key discoveries in oncogenes, tumor suppressor genes, and immune evasion strategies have led to the development of targeted therapies and immunotherapies. These advancements have revolutionized the treatment landscape, with therapies like immune checkpoint inhibitors, CAR T-cell therapy, and personalized medicine offering improved patient outcomes. However, challenges such as tumor heterogeneity, acquired drug resistance, therapy-related toxicities, and the high costs of these novel treatments continue to limit their effectiveness and accessibility. The review also delves into emerging therapeutic strategies, including next-generation immunotherapies, precision oncology enhanced by artificial intelligence, tumor vaccines, microbiome-based therapies, and the application of nanotechnology for drug delivery. As cancer therapies evolve, addressing these challenges is crucial for future breakthroughs. The review emphasizes the need for continued research into overcoming resistance mechanisms, reducing treatment-related side effects, and enhancing global access to cutting-edge treatments. Looking ahead, the integration of new technologies and the development of more equitable healthcare strategies will be essential to ensuring that advances in cancer therapy translate into improved survival and quality of life for patients worldwide. In conclusion, while remarkable progress has been made in cancer treatment, a multifaceted approach that blends scientific innovation, precision medicine, and healthcare accessibility will be key to overcoming the ongoing challenges in the fight against cancer. Keywords: Cancer Mechanism, Therapy, Advances, Challenges, Future Directions

Lenvatinib plus pembrolizumab versus chemotherapy as first-line therapy for advanced or recurrent endometrial cancer: Primary results of the phase III ENGOT-En9/LEAP-001 study

Lenvatinib plus pembrolizumab versus chemotherapy as first-line therapy for advanced or recurrent endometrial cancer: Primary results of the phase III ENGOT-En9/LEAP-001 study

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated Non-Small Cell Lung Cancer: An ATOMIC Registry Analysis

IntroductionOsimertinib is now a standard 1L therapy for EGFR-mutated advanced non-small cell lung cancer (NSCLC). We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC. MethodsPatients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator’s Consortium (ATOMIC) were included; demographic and clinical data including treatment patterns were described. Analyses of overall survival (OS), time to next treatment (TTNT), and incident brain and liver metastasis were performed on patients who started 1L therapy in ≥2015 using Kaplan-Meier method, Cox regression, and cumulative incidence functions. ResultsThe full cohort included 1,132 patients; mean age 63.4 years, 53% White, 68% female, 67% nonsmoker; 830 patients received 1L systemic therapy in ≥2015. The predominant first EGFR-TKI was erlotinib (65%) prior to 2018 and osimertinib (81%) after 2018. The median TTNT after start of 1L therapy was 13.9 months overall, and longest in patients receiving 1L osimertinib (28 months). In the post 2015 cohort, the baseline prevalence of brain metastasis (BM) was 54% and among patients without baseline brain metastasis, the probability of incident BM at 12, 24, and 48 months was 8%, 22% and 44%, respectively. Development of an on-treatment brain metastasis among patients without baseline brain metastasis was associated with a 3.2 times higher risk of death. ConclusionEven in a contemporary era with prevalent osimertinib use, baseline and longitudinal risk of BM development was high. The ongoing risk of developing BM, together with the associated survival detriment, argues for routine surveillance brain MRIs for patients with EGFRm NSCLC, which are not currently included in guidelines.

Geographic disparities in prescribing patterns of molecularly targeted therapy in advanced and recurrent endometrial cancer

Geographic disparities in prescribing patterns of molecularly targeted therapy in advanced and recurrent endometrial cancer

Regression and growth rates in androgen deprivation therapy for advanced castration-sensitive prostate cancer.

No study has compared cancer regression (d) and growth (g) rates in patients with advanced castration-sensitive prostate cancer (CSPC) treated with androgen deprivation therapy. The comparison of d and g rates provides insight into the differential impact of ADT regimens on tumor dynamics, potentially guiding more personalized treatment strategies. Therefore, we aimed to estimate these rates and evaluate their impact on survival outcomes. Sequential prostate-specific antigen (PSA) data was obtained from the KYUCOG-1401 trial including patients with advanced CSPC randomized to gonadotropin-releasing hormone (GnRH) antagonist (group A) and GnRH agonist plus bicalutamide (group B). d and g rates were estimated by applying mathematical models and were compared in subgroups. PSA-progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were compared by lower and higher than the median of these rates. Patients with higher PSA and higher extent of disease score at enrollment presented higher d rates (0.03965 vs. 0.03546, p = 0.0006) and (0.03947 vs. 0.03587, p = 0.0113) for groups A and B, respectively. The median d rate was lower for group A than group B (0.03306 vs. 0.039965, respectively [p = 0.0002]). The median g rate was higher for group A than group B (0.00016 vs. 0.00002, respectively [p = 0.0014]). The g rate, but not the d rate discriminated PSA-PFS, rPFS, and OS. Our results suggest that GnRH agonist plus bicalutamide reduced PSA level faster and suppressed PSA rising longer than GnRH antagonist. Moreover, measuring the g rate can predict PSA-PFS, rPFS, and OS in patients with advanced CPSC treated with androgen deprivation therapy. These findings suggest that incorporating g rate measurements into clinical practice could improve prognostic accuracy and guide treatment decisions in advanced CSPC.

Anti-inflammatory and anti-cancer effects of polysaccharides from Antrodia cinnamomea: A review.

Antrodia cinnamomea (Ac), also known as "Niu-Chang-Chih" in Chinese, is a valuable fungus that has been widely used as medicine and food among indigenous people in Taiwan. Ac is rich in polysaccharides (Ac-PS), making it a promising candidate for adjunctive therapy in cancer and inflammation conditions. There are two types of Ac-PS: general (non-sulfated) PS (Ac-GPS) and sulfated PS (Ac-SPS). This review highlights that both Ac-GPS and Ac-SPS possess immunomodulatory, anti-inflammatory and anti-cancer properties. Each type influences interleukin signaling pathways to exert its anti-inflammatory effects. Ac-GPS is particularly effective in alleviating inflammation in the brain and liver, while Ac-SPS shows its efficacy in macrophage models. Both Ac-GSP and Ac-SPS have demonstrated anti-cancer effects supported by in vitro and in vivo studies, primarily through inducing apoptosis in various cancer cell lines. They may also synergize with chemotherapy and exhibit anti-angiogenic properties. Notably, Ac-SPS appears to have superior anti-cancer efficacy, potentially due to its sulfate groups. Furthermore, Ac-SPS has been more extensively studied in terms of its mechanisms and effects on lung cancer compared with Ac-GPS, highlighting its significance in cancer research. In addition, Ac-SPS is often reported for its ability to activate macrophage-mediated responses. Clinically, Ac-GPS has been used as an adjunctive therapy for advanced lung cancer, as noted in recent reports. However, given the numerous studies emphasizing its anti-cancer mechanisms, Ac-SPS may exhibit greater efficacy, warranting further investigation. This review concludes that Ac-derived Ac-GPS or Ac-SPS have the potential to be developed into functional health supplements or adjunctive therapies, providing dual benefits of anti-inflammatory and anti-cancer effects.

Correlative study to assess the predictive power of the ICOS HF calculator in the prediction of development of HER-2 antagonist induced cardiac dysfunction in a single center in Saudi Arabia in 2023

Abstract Background Over the past 3 decades, there has been a significant increase in cancer survivors supported by the major advances in cancer therapies. However, most of those therapies are cardio-toxic. In 2022, the European Society of cardiology had published, for the first time, a clinical guideline that describes how to manage this cohort of patients, and endorsed the utilization of a risk calculator to predictor likelihood of development of cancer therapy cardiac dysfunction (CRTCD). We did retrospective review of all consecutive patients that have received Trstuzumab (HER-2 antagonist) in the year 2023 in a single tertiary cardiac center. We assessed their demographics and co-morbidities, incidence of CRTCD, evaluated their ICOS-HF score and looked for any CRTCD in this cohort to assess whether the calculated stratification correlated with development of CRTCD. The objective is to assess the utilization of this tool in our patient population. Methods 369 unique individuals were identified from the hospital databas that had received HER-2 antagonists. Basic patient demographics were extracted from the information system along with their clinical, laboratory, and echocardiographic data. Their risk profiles were stratified using the ICOS-HF calculator. Follow up echocardiogrphic studies were reviewed to assess the incidence of CRTCD in patients receiving HER-2 antagonists and the correlation between the risk strata using the ICOS-HF and actual development of CRTCD. Results The average age was 53+/- 11 years. 96.8% were females. At baseline, 20% were diabetic, 26.8% were hypertensive, 10.8% were dyslipidemic, 1.9% had prior cardiomyopathy or heart failure, 1.3% had IHD, 1.1% were smoker, 33.3% were obese, and 3.8% had CKD. Overall, in the year 2023, the incidence of HER-2 induced cardiac dysfunction was 10.6%. At baseline, using the ICOS-HF calculator, 57.9% were stratified as low risk, 21% as moderate risk 14.6% as high risk, and 6.5% as very high risk. Approximately 5% of the patients with low to moderate risk developed CRTCD, which rose to 18.5% in the high risk, and significantly rose to 58% in the very high risk population. Conclusion The risk stratification using the ICOS-HF calculator in consecutive patients receiving Trastuzumab correlated directly with the likelihood of developing CRTCD. 58% of all of the patients in the very high risk category developed CRTCD. This retrospective analysis validates the use of this tool in our patient population and will aid in the identification of patients that would require to have a more aggressive preemptive management, especially in the high and very high risk population using a multidisciplinary cardio-oncology team to optimize their surveillance and reduce their likelihood of cardiac dysfunction.

Clinical evaluation and outcome in patients with heart failure receiving chemotherapy with different anti-cancer agents

Abstract Background Over the last few decades, advances in cancer therapy have prolonged the life expectancies of patients diagnosed with malignancies. Although traditional cytotoxic chemotherapy, molecularly targeted therapy, and immunotherapy have improved survival rates, off-target adverse effects such as complications of the cardiovascular system require attention. The optimal strategy for modern chemotherapy should be based on a comprehensive approach for patients with cancer and cardiovascular diseases. Therefore, cardio-oncology has received increasing attention owing to the cardiotoxic effects of anti-cancer therapies. Purpose To assess the clinical characteristics and outcomes of patients with heart failure (HF) who received chemotherapy compared with those of a matched cohort with HF who did not receive chemotherapy, using real-world HF data. Methods This study used the Diagnosis Procedure Combination database of the Japanese Registry of All Cardiac and Vascular Disease. We identified 1,328,113 patients hospitalized for HF between April 2012 and March 2021. We excluded 14,043 patients with unknown outcomes, non-emergency admissions, and unknown chemotherapy data. The primary endpoint was readmission. Thus, our study included 5,774 patients who received chemotherapy and 39,412 patients who did not. The propensity score (PS) was estimated using a logistic regression model, with chemotherapy as the dependent variable, and clinically score-matched analysis of 11,532 patients with HF with or without chemotherapy. Results Colon, lung, breast, and prostate cancers accounted for > 60% of all cancer types. After PS matching, 62.5% and 19.5% of patients with HF had prostate and breast cancer, respectively. After PS matching, readmission was more frequently observed in patients undergoing chemotherapy than those not undergoing chemotherapy (odds ratio [OR], 1.26; 95% confidence interval [CI] 1.17–1.36, p<0.0001). Treatment with genomic epidermal growth factor receptor tyrosine kinase inhibitors (OR, 1.69; 95% CI 1.39–2.07), taxane (OR, 2.95; 95% CI 2.11–4.12), anthracyclines (OR, 1.86; 95% CI 1.19–2.90), and fluorouracil agents (OR, 1.65; 95% CI 1.18–2.30) resulted in a significant risk of readmission. Moreover, patients treated with endocrine therapy before hospitalization had significantly higher readmission rates than the matched patients who did not receive chemotherapy (aromatase inhibitors: OR, 1.40; 95% CI 1.19–1.65: anti-androgens: OR, 1.39; 95% CI 1.27–1.52: luteinizing hormone-releasing hormone agonists: OR, 1.18; 95% CI 1.08–1.30 and gonadotropin-releasing hormone antagonists: OR, 2.17; 95% CI 1.68–2.79). Conclusions Medical providers need to monitor and follow-up patients with HF, depending on the characteristics of the anticancer agents and types of cancer. Furthermore, close collaboration among oncologists, cardiologists, and healthcare professionals will ensure the delivery of optimal care for patients with HF undergoing chemotherapy.

The present and future of the Cancer Dependency Map.

Despite tremendous progress in the past decade, the complex and heterogeneous nature of cancer complicates efforts to identify new therapies and therapeutic combinations that achieve durable responses in most patients. Further advances in cancer therapy will rely, in part, on the development of targeted therapeutics matched with the genetic and molecular characteristics of cancer. The Cancer Dependency Map (DepMap) is a large-scale data repository and research platform, aiming to systematically reveal the landscape of cancer vulnerabilities in thousands of genetically and molecularly annotated cancer models. DepMap is used routinely by cancer researchers and translational scientists and has facilitated the identification of several novel and selective therapeutic strategies for multiple cancer types that are being tested in the clinic. However, it is also clear that the current version of DepMap is not yet comprehensive. In this Perspective, we review (1) the impact and current uses of DepMap, (2) the opportunities to enhance DepMap to overcome its current limitations, and (3) the ongoing efforts to further improve and expand DepMap.

Case report: Long-term progression-free survival in advanced ovarian cancer treated with apatinib in first-line maintenance treatment

Ovarian cancer is one of the most common gynecological malignancies. The current first-line treatment strategies for advanced ovarian cancer include surgery, chemotherapy, and maintenance therapy. Bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) are primary maintenance treatments for advanced ovarian cancer. Previously, many patients declined these therapies before medicare coverage because of high costs. Bevacizumab and apatinib are anti-tumor angiogenic agents. In this case study, we describe a patient with advanced ovarian cancer who underwent neoadjuvant chemotherapy, interval debulking surgery, and adjuvant chemotherapy. She declined bevacizumab and PARPi maintenance therapy owing to the prohibitive expenses. The patient was administered off-label apatinib and achieved a progression-free survival of 54 months. Thus, apatinib may offer substantial therapeutic value as a first-line maintenance therapy in advanced ovarian cancer.

Pemetrexed-carboplatin salvage therapy in advanced thyroid cancers.

The overall survival of patients with advanced thyroid cancers that have progressed following targeted therapies is limited, indicating a strong need for salvage treatments. We retrospectively analyzed patients with refractory advanced thyroid cancer treated with pemetrexed-carboplatin (PC) at Mayo Clinic since 2019. Eleven patients, three with anaplastic thyroid cancer (ATC), seven with differentiated or poorly differentiated thyroid cancer (DTC), and one with oncocytic carcinoma of the thyroid, were treated with novel salvage PC. Patients with DTC (n = 7) had durable responses with a median progression-free survival of 29 months. One responder included a patient with ATC whose disease progressed following pembrolizumab/axitinib, lenvatinib, and dabrafenib/trametinib. On this fourth line treatment, the patient remains on therapy to date, over 12 months after initial response. This case series reinforces prior published phase I clinical trial data and shows that pemetrexed can have potent efficacy in the treatment of the most advanced thyroid cancers.