Oxaliplatin-induced Acute Neurotoxicity Recovers Between Repeat Infusion Cycles: An Axonal Excitability Repeated Multiple Measurements Study.

Background/Aim: Oxaliplatin, a platinum-based chemotherapy used in the treatment of colorectal cancer, induces acute neurotoxicity following infusion. The aim of this study was to establish whether alterations in axonal excitability develop progressively with higher cumulative doses and whether there is a recovery in motor axons after each cycle of treatment. Patients and Methods: Twenty consecutive patients with a colorectal cancer diagnosis, referred from the Oncology Department of Aretaieion Hospital of Athens, were enrolled in this study between October 2018 and May 2019. None of the participants had diabetes, alcohol abuse, known neuropathy or were previously treated with another neo-adjuvant therapy. Threshold Tracking techniques and Qtrac software were used for assessing axonal excitability in motor axons. Excitability recordings were undertaken before and immediately after the end of oxaliplatin infusion. Results: Statistically significant changes were found (p<0.01) in axonal excitability (relative refractory period, refractoriness at 2 ms and 2.5 ms, sub-excitability and super-excitability) before and after oxaliplatin infusion. No statistically significant changes (p>0.05) were found in threshold electrotonus and strength-duration parameters before and after oxaliplatin infusion. We also did not find statistically significant differences (p>0.05) between means of excitability parameters before infusion at each cycle. Conclusion: Our study confirms oxaliplatin-induced acute neurotoxicity following infusion and suggests that motor axons recover between repeat infusion cycles.

Impact of CDK4/6 Inhibitors on Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS) in the Adjuvant Setting.

Background: Third-generation aromatase inhibitors (AIs) are the mainstay of treatment in hormone receptor (HR)-positive breast cancer. Even though it is considered to be a well-tolerated therapy, AI-induced musculoskeletal symptoms are common and may be accused for treatment discontinuation. Recently, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors changed the therapeutic setting, and currently, ribociclib, palbociclib, and abemaciclib are all approved in combination with nonsteroidal AIs in patients with ER-positive, HER2-negative advanced or metastatic breast cancer. This systematic review aims to identify the frequency of aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) in the adjuvant setting in patients under AI monotherapy compared to patients under combination therapy with AIs and CDK4/6 inhibitors and demonstrate the underlying mechanism of action. Methods: This study was performed in accordance with PRISMA guidelines. The literature search and data extraction from all randomized clinical trials (RCTs) were done by two independent investigators. Eligible articles were identified by a search of MEDLINE and ClinicalTrial.gov database concerning the period 2000/01/01-2021/05/01. Results: Arthralgia was reported in 13.2 to 68.7% of patients receiving AIs for early-stage breast cancer, while arthralgia induced by CDK4/6 inhibitors occurred in a much lower rate [20.5-41.2%]. Bone pain (5-28.7% vs. 2.2-17.2%), back pain (2-13.4% vs. 8-11.2%), and arthritis (3.6-33.6% vs. 0.32%) were reported less frequently in patients receiving the combination of CDK4/6 inhibitors with ET. Conclusions: CDK4/6 inhibitors might have a protective effect against joint inflammation and arthralgia occurrence. Further studies are warranted to investigate arthralgia incidence in this population.

Pembrolizumab in combination with bevacizumab and oral cyclophosphamide in heavily pre-treated platinum-resistant ovarian cancer.

OBJECTIVE: Immune checkpoint inhibitors have been widely implemented in the treatment of solid tumors. Combinations of immune checkpoint inhibitors with chemotherapy, anti-vascular endothelial growth factor (VEGF) compounds, and poly-adenosine diphosphate-ribose polymerase inhibitors (PARP) are under evaluation in ovarian cancer. We aim to explore the efficacy of pembrolizumab in combination with bevacizumab and oral cyclophosphamide in patients with recurrent epithelial ovarian cancer. METHODS: This was a retrospective study of all patients who received pembrolizumab in combination with bevacizumab and oral cyclophosphamide for recurrent platinum-resistant heavily pre-treated ovarian cancer in the Oncology Unit of Alexandra University Hospital from January 2021 to July 2022. RESULTS: Median age at diagnosis was 56 years (SD 9.2; range 37-72). All patients were diagnosed with high-grade serous ovarian carcinoma. Initial disease stage was International Federation of Gynecology and Obstetrics (FIGO) IIIC in most cases (11/15, 73%). Patients were heavily pre-treated with a median of six (range 4-9) prior lines of systemic therapy. All patients experienced disease progression on first-line platinum-based chemotherapy, and median progression-free survival on first-line treatment was 22 months (95% CI 10.6 to 33.4). Patients received a median of four cycles of pembrolizumab in combination with cyclophosphamide and bevacizumab (range 3-20). Overall response rate was 13% (2/15) and disease control rate was 33% (5/15) with two patients achieving partial response and three patients achieving stable disease. Median progression-free survival was 3.5 months (95% CI 1.3 to 5.7) and the 6-month progression-free survival rate was 20%. Treatment was well tolerated with no dose-limiting toxicities. CONCLUSION: We showed that the combination of pembrolizumab with bevacizumab and oral cyclophosphamide is an effective alternative in heavily pre-treated patients with ovarian cancer who have otherwise limited treatment options.

Assessment of Postvaccination Neutralizing Antibodies Response against SARS-CoV-2 in Cancer Patients under Treatment with Targeted Agents.

The administration of a third dose of a vaccine against SARS-CoV-2 has increased protection against disease transmission and severity. However, the kinetics of neutralizing antibodies against the virus has been poorly studied in cancer patients under targeted therapies. Baseline characteristics and levels of neutralizing antibodies at specific timepoints after vaccination were compared between patients suffering from breast, ovarian or prostate cancer and healthy individuals. Breast cancer patients were treated with cyclin D kinase 4/6 inhibitors and hormonal therapy, ovarian cancer patients were treated with poly (ADP-ribose) polymerase inhibitors and prostate cancer patients were treated with an androgen receptor targeted agent. Levels of neutralizing antibodies were significantly lower in cancer patients compared to healthy individuals at all timepoints. Antibodies' titers declined over time in both groups but remained above protective levels (>50%) at 6 months after the administration of the second dose. The administration of a third dose increased neutralizing antibodies' levels in both groups. The titers of protective against SARS-CoV-2 antibodies wane over time and increase after a third dose in cancer patients under treatment.

SARS-CoV-2 Neutralizing Antibodies Kinetics Postvaccination in Cancer Patients under Treatment with Immune Checkpoint Inhibition.

Considering that COVID-19 could adversely affect cancer patients, several countries have prioritized this highly susceptible population for vaccination. Thus, rapidly generating evidence on the efficacy of SARS-CoV-2 vaccination in the subset of patients with cancer under active therapy is of paramount importance. From this perspective, we launched the present prospective observational study to comprehensively address the longitudinal dynamics of immunogenicity of both messenger RNA (mRNA) and viral vector-based vaccines in 85 patients treated with immune checkpoint inhibitors (ICIs) for a broad range of solid tumors. Despite the relatively poor humoral responses following the priming vaccine inoculum, the seroconversion rates significantly increased after the second dose. Waning vaccine-based immunity was observed over the following six months, yet the administration of a third booster dose remarkably optimized antibody responses. Larger cohort studies providing real-world data with regard to vaccines effectiveness and durability of their protection among cancer patients receiving immunotherapy are an increasing priority.

Immunological Response to COVID-19 Vaccination in Ovarian Cancer Patients Receiving PARP Inhibitors.

OBJECTIVE: Vaccination for SARS-CoV-2 provides significant protection against the infection in the general population. However, limited data exist for cancer patients under systemic therapy. METHODS: In this cohort, we prospectively enrolled cancer patients treated with PARPi as well as healthy volunteers in order to study the kinetics of anti-SARS-CoV-2 antibodies (NAbs) after COVID-19 vaccination. Baseline demographics, co-morbidities, and NAb levels were compared between the two groups. RESULTS: The results of the cohort of 36 patients receiving PARP inhibitors are presented here. Despite no new safety issues being noticed, their levels of SARS-CoV-2 neutralizing antibodies were significantly lower in comparison to matched healthy volunteers up to day 30 after the second dose. CONCLUSIONS: These results suggest that maintaining precautions against COVID-19 is essential for cancer patients and should be taken into consideration for the patients under treatment, while further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.

CDK4/6 Inhibitors and Arthralgia: A Single Institution Experience.

BACKGROUND: Aromatase inhibitors (AIs) are associated with musculoskeletal pain in one third (20-47%) of breast cancer patients. Recently, CDK4/6 inhibitors have emerged as a new therapeutic approach in hormone receptor (HR)-positive breast cancer. While hematological and gastrointestinal toxicities are frequently reported during treatment with CDK4/6 inhibitors, musculoskeletal symptoms are less commonly encountered. METHODS: Herein, we present a retrospective study of 47 breast cancer patients who received CDK4/6 inhibitors along with endocrine therapy in our department between 01/01/2018 and 01/09/2020. RESULTS: Median age at diagnosis was 58 years (29-81). Median duration of treatment was 8.76 months (SD: 7.68; 0.47-30.13 months). Median PFS was 24.33 months (95% CI; 1.71-46.96). Overall, toxicity was reported in 61.7% of the cases (29/47). Arthralgia was reported in 6.4% (3/47) of the patients. Hematological toxicity was reported in 51.1% (24/47) of the patients. Neutropenia was the main hematological toxicity observed (86.8%; 22/47) along with anemia (4.3%; 2/47), thrombocytopenia (2.1%; 1/47), and leukopenia (4.2%; 1/24). CONCLUSIONS: Though our data reflect a small sample size, we report a reduced arthralgia rate (6.4%) during treatment with CDK4/6 inhibitors compared with that reported in studies of AIs (20-47%).

Secondary Alopecia Neoplastica Mimicking Alopecia Areata following Breast Cancer.

Cutaneous metastases from visceral carcinomas are relatively uncommon, with an overall incidence ranging from 0.7 to 9%. Diagnosis of scalp metastases usually escapes clinicians and dermatologists due to the fact that these metastases are mimicking other benign dermatological conditions. Herein, we present an uncommon case of scalp alopecia neoplastica mimicking alopecia areata due to breast cancer; a 43-year-old woman diagnosed with lobular cancer 3 years previously presented with acute loss of hair in well-circumscribed areas of the scalp and was diagnosed with alopecia areata by a private-practice dermatologist. She was then reevaluated, and due to her history of breast cancer, a biopsy from the scalp was performed and revealed alopecia neoplastica. At the same time that the skin lesions were recognized as disease involvement, the patient presented with dyspepsia, and endoscopy of the upper and lower gastrointestinal tract also revealed metastasis to the stomach and bowel. Gastrointestinal metastasis may occur with several types of cancer, but the stomach and bowel are rare metastatic sites for breast cancer.