BACKGROUND:There is limited real-world data on the use of CDK4/6 inhibitors in Australian patients with HR+/HER2- advanced or metastatic breast cancer. This study describes the demographic and clinical characteristics of patients initiating CDK4/6 inhibitors, and analyses of real-world treatment patterns and outcomes with palbociclib, including dose modifications, time to chemotherapy initiation, and duration of treatment. METHODS:This non-interventional retrospective cohort study from Australia used the Pharmaceutical Benefits Scheme dataset, which includes longitudinal claims data from January 2004 to December 2023. The study population comprised CDK4/6i-naïve patients aged ≥ 18 years initiating first treatment with a CDK4/6 inhibitor between June 2018 and December 2023. Comorbidities were determined using the validated Rx-Risk Comorbidity Index. Descriptive data analyses were conducted, and the Kaplan-Meier method was used for time-to-event analyses. RESULTS:The study analyzed data from 1128 patients, including 407 initiating palbociclib. The median age at palbociclib initiation was 67 years, with 67% aged > 60 years. Sixty seven percent of patients had received treatment for ≥ 3 comorbidities in the preceding 12 months. 80% of patients started on the 125-mg formulation, and 53% did not undergo a dose modification (all initiated doses). At a median follow-up of 38 months, 61% and 40% remained on treatment with palbociclib at 12 and 24 months, respectively. Median duration of treatment was 541 days (18 months) and median time to chemotherapy was not reached. CONCLUSIONS:This study provides real-world data on the utilization and outcomes of palbociclib in Australia, complementing data from randomized clinical trials and offering insights into the management of HR+/HER2- advanced or metastatic breast cancer. TRIAL REGISTRATION:ClinicalTrials.Gov identifier: NCT06624020.

Advances in human epidermal growth factor receptor 2 (HER2)-directed therapies have revolutionised the care of patients with HER2-positive breast cancer. While adjuvant trastuzumab in combination with chemotherapy has dramatically improved the prognosis for patients with early-stage disease, up to a quarter of patients will develop recurrent disease. The standard-of-care treatment paradigm has evolved with the introduction of newer HER2-directed therapies and increasing use of neoadjuvant systemic therapy, the latter providing us with important functional data to HER2-directed therapies and impacting subsequent adjuvant therapy decisions. However, these new strategies come at a cost of increased toxicity and economic burden, and only a subset of patients benefit from such approaches. Thus, ongoing work is required to identify predictive biomarkers of response, to de-escalate treatment in patients who may do just as well with less therapy, and new therapeutic approaches for patients who do not respond to currently used therapies. In this review, we will examine the current therapeutic landscape, summarise the latest evidence, and list the current treatment algorithms for early stage HER2-positive breast cancer.

Background: Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side-effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids, platinum analogues, and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine, and antidepressants have had limited efficacy and may themselves induce adverse side-effects. Methods: To determine the potential use of herbal medicines as adjuvants in cancer treatments, a critical literature review was conducted by electronic and manual search on nine databases. These include PubMed, the Cochrane Library, Science Direct, Scopus, EMBASE, MEDLINE, Google Scholar, and two Chinese databases CNKI and CINAHL. Thirty-four studies were selected from 5614 studies assessed and comprising animal studies, case reports, retrospective studies, and minimal randomized clinical trials investigating the anti-CIPN effect of herbal medicines as the adjuvant intervention in patients administered chemotherapy. The thirty-four studies were assessed on methodological quality and limitations identified. Results: Studies were mixed in their recommendations for herbal medicines as an adjuvant treatment for CIPN. Conclusion: Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. Given that the number of cancer survivors is increasing, the long-term side effects of cancer treatment, is of major importance.

Purpose of Review The purpose of this mini review is to evaluate the literature on B vitamins and chemotherapy-induced peripheral neuropathy. Recent Findings One hundred and five journal articles were evaluated and nine manuscripts were included. There was one in vitro, one was an animal and seven were human studies. The in vitro study was a safety study on vitamin B 6 and oxaliplatin which was not directly related to CIPN. The animal study evaluated vitamin B 3 on paclitaxel administration with positive results. The human studies varied using a vitamin B complex, vitamin B 12 only and vitamin B 6 . Summary Chemotherapy-induced peripheral neuropathy (CIPN) continues to plague patients and the medical fraternity. Currently, there are still no conclusive protective or treatment options. B vitamins have been found to play a role in CIPN prevention, but further studies are required to ascertain possible protection and treatment options.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect resulting from neurotoxic chemotherapeutic agents. This study aimed to assess the efficacy and safety of an oral B group vitamin compared to placebo, in preventing the incidence of CIPN in cancer patients undergoing neurotoxic chemotherapy.

154 Background: Neurological complications such as chemotherapy-induced peripheral neuropathy (CIPN) and neuropathic pain are frequent side-effects of neurotoxic chemotherapy agents. An increasing survival rate and frequent administration of adjuvant chemotherapy treatments involving neurotoxic agents makes it imperative that accurate diagnosis, prevention and treatment of these neurological complications be implemented to minimize the burden experienced by patients undergoing these treatments.METHODSTo determine the potential use of pharmaceuticals, nutraceuticals and herbal medicines as adjuvants in cancer treatments a critical literature review was conducted by electronic and manual search on nine databases. These include PubMed, the Cochrane Library, Science Direct, Scopus, EMBASE, MEDLINE, Google Scholar and two Chinese databases CNKI and CINAHL. Thirty studies were selected for pharmaceutical agents, twenty-four studies for nutraceuticals and thirty-four studies for herbal medical trials. Seven acupuncture trials were also identified in relation to CIPN management. Data was collated and organised into chemotherapy drugs, agent's trialled, number of participants, results and recommendations.RESULTSFor pharmaceutical agents, amifostine has possible ototoxicity protection for children in cisplatin and duloxetine as a treatment option for pain. For nutraceuticals, vitamin E was found to have protective abilities for cisplatin ototoxicity, omega 3 fatty acids for taxane administration and vitamin B6 and lipoic acid for oxaliplatin CIPN. In herbal medicine, Goshajinkigan showed great promise for oxaliplatin-IPN protection. Vitamin B12 deficiencies have also been found to increase the onset and severity of CIPN.CONCLUSIONSCurrently, no pharmaceutical, nutraceutical or complementary agent has been found to be completely beneficial in preventing or treating CIPN. It is suggested clinicians identify the best option from the research to assist patients in both possible prevention and treatment of CIPN. In addition, research has found that a vitamin B12 deficiency may potentiate moderate to severe CIPN presentation and testing of this vitamin is suggested.

Objective: Neurological complications such as chemotherapy-induced peripheral neuropathy (CIPN) and neuropathic pain are frequent side effects of neurotoxic chemotherapy agents. An increasing survival rate and frequent administration of adjuvant chemotherapy treatments involving neurotoxic agents makes it imperative that accurate diagnosis, prevention, and treatment of these neurological complications be implemented. Methods: A consideration was undertaken of the current options regarding protective and treatment interventions for patients undergoing chemotherapy with neurotoxic chemotherapy agent or experience with CIPN. Current knowledge on the mechanism of action has also been identified. The following databases PubMed, the Cochrane Library, Science Direct, Scopus, EMBASE, MEDLINE, CINAHL, CNKI, and Google Scholar were searched for relevant article retrieval. Results: A range of pharmaceutical, nutraceutical, and herbal medicine treatments were identified that either showed efficacy or had some evidence of efficacy. Duloxetine was the most effective pharmaceutical agent for the treatment of CIPN. Vitamin E demonstrated potential for the prevention of cisplatin-IPN. Intravenous glutathione for oxaliplatin, Vitamin B6 for both oxaliplatin and cisplatin, and omega 3 fatty acids for paclitaxel have shown protection for CIPN. Acetyl-L-carnitine may provide some relief as a treatment option. Acupuncture may be of benefit for some patients and Gosha-jinki-gan may be of benefit for protection from adverse effects of oxaliplatin induced peripheral neuropathy. Conclusions: Clinicians and researchers acknowledge that there are numerous challenges involved in understanding, preventing, and treating peripheral neuropathy caused by chemotherapeutic agents. New insights into mechanisms of action from chemotherapy agents may facilitate the development of novel preventative and treatment options, thereby enabling medical staff to better support patients by reducing this debilitating side effect.

The authors regret that the caption for Figure 1 should have cited reference 6 (Park SB et al. Mechanisms underlying chemotherapy-induced neurotoxicity and the potential for neuroprotective strategies. Curr Med Chem 2008; 15:3081–94) as the source of the figure, rather than reference 7. The image is reproduced from reference 6 with permission.The authors would like to apologise for any inconvenience caused. The authors regret that the caption for Figure 1 should have cited reference 6 (Park SB et al. Mechanisms underlying chemotherapy-induced neurotoxicity and the potential for neuroprotective strategies. Curr Med Chem 2008; 15:3081–94) as the source of the figure, rather than reference 7. The image is reproduced from reference 6 with permission. The authors would like to apologise for any inconvenience caused. Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): A systematic reviewClinical NutritionVol. 32Issue 6PreviewChemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. Full-Text PDF

9604 Background: Chemotherapy induced peripheral neuropathy [CIPN] is a debilitating side effect resulting from the administration of neurotoxic chemotherapy agents. It is estimated that a third of all patients undergoing chemotherapy experience CIPN, with a third of those progressing to a permanent neuropathy. Patients experiencing moderate to severe CIPN report reduced quality of life, chronic discomfort and disruption of physical abilities for general life activities which can be temporary or permanent. Moreover, CIPN can lead to a dose reduction or possible cessation of treatment, which may adversely impact disease outcomes. Methods: In a randomised placebo-controlled trial, newly diagnosed patients undergoing chemotherapy treatment with paclitaxel, oxaliplatin or vincristine were assessed for the safety and efficacy of an oral B group vitamin to reduce the incidence of CIPN. The primary outcome was the TNS and secondary outcomes included B vitamin pathology, EORTC QoL, Brief Pain Inventory and PNQ. Results: A total of 71 subjects were randomised from 121 evaluable patients (B vitamin n = 38; placebo n = 33). Participants between groups were matched for gender, chemotherapy agents, age and BMI. No statistical significance was found for the prevention of CIPN from vitamin B supplementation through total TNS score (p = 0.73). Statistical significance was recorded for sensory peripheral neuropathy in the PNQ (12 weeks p = 0.03; 24 weeks p = 0.005; 36 weeks p = 0.021). The risk estimate for the PNQ was also statistically significant with an OR = 5.78, 95% CI = [1.63-20.5]. Conclusions: B vitamin supplementation throughout chemotherapy administration was not superior to placebo (p > 0.05) for the prevention of CIPN. Patient perception of reduced sensory peripheral neuropathy with B vitamin supplementation over placebo was statistically significant. Although not significant a trend was observed for the prevention of the onset and severity of CIPN throughout chemotherapy with B vitamins supplementation over placebo. Furthermore, patients with moderate to severe CIPN may have a vitamin B12 deficiency that may lead to a worse symptomatic presentation. Clinical trial information: 12611000078954.

Improvements in the treatment of metastatic HER2-positive breast cancer constitute one of the great advances in breast cancer medicine of the last generation. From being a highly aggressive fatal condition, the use of anti-HER2-targeted therapies, in particular trastuzumab, has led to significant improvements in disease outcomes. There are reports of increasing numbers of patients alive and well more than 5 years from diagnosis of metastatic disease. Nevertheless, there remain many complex and clinically difficult scenarios where there is little in the way of randomized evidence or published guidelines to guide decision making. As a companion piece to our review of HER2-targeted therapies in the metastatic setting, we decided to focus on a series of clinical scenarios that fell outside of the standard trial-based settings and where opinions and guidance from experienced clinicians and experts in the field would be considered useful to help develop safe and effective treatment strategies. The following eight cases were put forward by our panel of experts, voted on by their peers to select the most relevant and interesting cases, and the discussions worked on by teams of two followed by review and commentary by another team of two.

AIM:We aimed to systematically review and summarize data from the available clinical trials that examined the treatment of HER2-positive metastatic breast cancer. METHODS:We reviewed phase 2 and 3 studies in which an anti-HER2 agent was used in one or both arms of the study. While formal meta-analysis was not possible for such a heterogeneous group of trials, resulting forest plots outline some generalizable findings. RESULTS:There is strong evidence that the addition of an anti-HER2 agent to standard chemo- or endocrine therapy improves clinically relevant measurable outcomes. There is also consistent evidence that initial treatment with trastuzumab alone (and subsequent use of a cytotoxic) is inferior to the initial combination of trastuzumab plus chemotherapy, and that either T-DM1 or dual anti-HER2 agents are superior to single anti-HER2 agent regimens. There is no strong evidence that the use of more than one cytotoxic agent together with an anti-HER2 agent confers any benefit over a single cytotoxic, anti-HER2 combination. CONCLUSION:This review provides a strong evidence base for current clinical practice with a discussion of treatment in the Australian setting.

Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made.

INTRODUCTION: CIPN is a significant debilitating side effect resulting from the administration of neurotoxic chemotherapy agents[1]. It is estimated that a third of all patients undergoing chemotherapy experience CIPN[2]. Patients experiencing moderate to severe CIPN report reduced quality of life[3], chronic discomfort[4] and disruption of physical abilities for general life activities which can be temporary or permanent[3]. Moreover, CIPN can lead to a dose reduction or possible cessation of treatment which may adversely impact disease outcomes[1,2]. METHODOLOGY A pilot trial assessing the safety and efficacy of an oral B group vitamin in newly diagnosed patients undergoing chemotherapy treatment with paclitaxel, oxalilplatin or vincristine for nine months. 140 patients will be randomly assigned to either a placebo group [n=70] or oral B group vitamin [n=70]. The primary outcome is the Total Neuropathy Score and secondary outcomes include B vitamin pathology, EORTC quality of life questionnaire, Brief Pain Inventory and Patient Neurotoxicity Questionnaire conducted T0 T12 T24 T36. DISCUSSION: It is hypothesised that therapeutic doses of B group vitamins will decrease the onset and severity of CIPN. Deficiencies in certain B group vitamins may promote nerve dysfunction and damage that can lead to peripheral neuropathy similar to CIPN[5]. Administration of B group vitamins has been found to reverse B vitamin deficiency induced peripheral neuropathy. To date, there are no published papers on oral B group vitamins and CIPN, however, B vitamin administration has benefited peripheral neuropathies from diabetes, HIV/AIDs, postgastrectomy and alcoholism. Two studies have been conducted on vitamin B6 and CIPN reporting beneficial results. CONCLUSIONS: Pilot data on 5 patients, three female and two males has shown reduced onset and severity of CIPN with oral B group vitamins throughout chemotherapy treatment. Preliminary absorption data on the B group vitamin supplement has shown positive results indicating that the B vitamins are absorbed.

Lung cancer remains a leading cause of disease globally, with smoking being the largest single cause. Phase I enzymes, including cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), are involved in the activation of carcinogens, such as polycyclic aromatic hydrocarbons, to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of the present study was to investigate the association of CYP1A1 gene polymorphisms and haplotypes with lung cancer risk. A case–control study was carried out on 1,040 nonsmall cell lung cancer (NSCLC) cases and 784 controls to investigate three CYP1A1 variants, CYP1A1*2A (rs4646903; thymidine to cytosine substitution at nucleotide 3801 (3801T>C)), CYP1A1*2C (rs1048943; 2455A>G; substitution of isoleucine 462 with valine (exon 7)) and CYP1A1*4 (rs1799814; 2453C>A; substitution of threonine 461 with asparagine (exon 7)) using PCR restriction fragment length polymorphism methods. The CYP1A1*2A and CYP1A1*2C variants were significantly over-represented in NSCLC cases compared with controls, whereas the CYP1A1*4 variant was under-represented. CYP1A1 haplotypes (in allele order CYP1A1*4, CYP1A1*2C, CYP1A1*2A) CGC and CGT were associated with an increased risk of lung cancer, whereas AAT was associated with decreased lung cancer risk in this population. The present study has identified risk haplotypes for CYP1A1 in NSCLC and confirmed that CYP1A1 polymorphisms are a minor risk factor for NSCLC.