Single agent vs combination immunotherapy in advanced melanoma: a review of the evidence.

PURPOSE OF REVIEW: The aim of this review is to outline the current landscape of advanced melanoma treatment options, provide insights on selecting combination therapies within different clinical scenarios, capture clinical relevance of anti-programmed cell death protein 1 (PD-1) monotherapy, and explore the unmet needs with immune check-point inhibitors (ICI) in advanced melanoma. RECENT FINDINGS: ICI based treatment consisted of single agent ICI or dual combination ICI-ICI is the standard of care of front-line treatment of metastatic or unresectable melanoma. PD-1 inhibitors (Pembrolizumab and Nivolumab) improved progression free survival (PFS) and overall survival (OS) compared to chemotherapy and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors (Ipilimumab and Tremelimumab). The dual ICI combination (Nivolumab and Ipilimumab) provided profound and durable responses better than monotherapy, and the longest overall survival ever achieved in advanced disease, including in patients with murine sarcoma viral oncogene homolog B (BRAF)-mutated disease, but at the cost of a high risk of severe toxicity. The new dual blockage of LAG-3 and PD-1 (Nivolumab-Relatlimab) emerges as a valid option with promising efficacy outcomes and a favourable toxicity profile. Mature survival data is still needed to capture the real benefit. SUMMARY: These new plethora of options pose new challenges not only for optimal treatment sequencing strategies but especially for management of adverse effects, endorsing the need to integrate a holistic and personalized approach for patient care.

Pazopanib-induced trismus in a young male with metastatic renal cell carcinoma: a case report and literature review.

The treatment landscape of advanced kidney cancer has radically changed over the years. Targeting tumor angiogenesis from historical cytokines to multi-tyrosine kinase inhibitors and recently the advent of immunotherapy resulted in a radical improvement in survival but presented substantial challenges in terms of toxicity management. In countries where the access to immune checkpoints inhibitors is still very limited, tyrosine-kinase inhibitors remain the optimal choice. The toxicity profile of these agents can influence both the clinician and the patient's preference for one molecule over another. This report describes the case of a young man treated with Pazopanib in a first-line setting for stage IV renal carcinoma who developed trismus under treatment. The occurrence of this off-target toxicity has made the patient ineligible for anti-angiogenic drugs. Although side effects of tyrosine kinase inhibitors seem manageable and reversible, some less known and unusual effects may evolve into severe and irreversible complications.

Non-operative management after immune checkpoint inhibitors for early-stage, dMMR/MSI-H gastrointestinal cancers.

Surgery is a standard treatment for early-stage gastrointestinal cancers, often preceded by neoadjuvant chemo(radio)therapy or followed by adjuvant therapy. While leading to cure in a proportion of patients, it has some drawbacks such as intra/post-operative complications, mutilation and life-long functional sequelae. Further to the unprecedented efficacy data from studies of immune checkpoint inhibitors for advanced mismatch repair deficient/microsatellite instable (dMMR/MSI-H) tumours, a strong interest has recently emerged for the investigation of such agents in the neoadjuvant setting. Although limited by the exploratory design and small sample size, trials of neoadjuvant immune checkpoint inhibitors for early-stage dMMR/MSI-H gastrointestinal cancers have consistently reported complete response rates ranging from 70 % to 100 %. As a result, the question has arisen as to whether surgery is still needed or organ-preserving strategies should be offered to this especially immuno-sensitive population. In this article, we discuss the available evidence for neoadjuvant immune checkpoint inhibitors in dMMR/MSI-H gastrointestinal cancers and analyse opportunities and challenges to the implementation of non-operative management approaches in this setting.

PD-L1 Expression in Paired Samples of Rectal Cancer.

Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS). Eighty-three patients were included. At diagnosis, PD-L1 expression ≥1%/≥5% was observed in 15.4%/0%, 80.7%/37.4%, and 69.2%/25.6% of patients based on TPS, ICS, and CPS, respectively. At surgery, the respective figures were 4.6%/1.5%, 60.2%/32.5%, and 50.7%/26.2%. Using the 1% cut-off and regardless of the scoring system, PD-L1 was less expressed in surgery than biopsy samples (p ≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy (p = 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17; p = 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19; p = 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28; p = 0.04) or ≥5% (HR 0.19; p = 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20; p = 0.04) were associated with better overall survival. Our study suggests that PD-L1 expression in RC is largely reflective of immune cell infiltration, and its presence/increase in surgical samples predicts better outcomes.

Conflict of Interest Disclosure in Oncology: Preliminary Insights From the Global ONCOTRUST-1 Cross-Sectional Study.

PURPOSE: Conflicts of interest (COIs) between oncologists and industry might considerably influence how the presentation of the research results is delivered, ultimately affecting clinical decisions and policy-making. Although there are many regulations on reporting COI in high-income countries (HICs), little is known about their reporting in low- and middle-income countries (LMICs). Oncology Transparency Under Scrutiny and Tracking (ONCOTRUST-1) is a pilot global survey to explore the knowledge and perceptions of oncologists regarding COI. MATERIALS AND METHODS: We designed an online 27-question-based survey in the English language to explore the perceptions and knowledge of oncologists regarding COI, with an emphasis on LMICs. Descriptive statistics and the Consensus-Based Checklist for Reporting of Survey Studies guidelines were used to report the findings. RESULTS: ONCOTRUST-1 surveyed 200 oncologists, 70.9% of them practicing in LMICs. Median age of the respondents was 36 (range, 26-84) years; 47.5% of them were women. Of the respondents, 40.5% reported weekly visits by pharmaceutical representatives to their institutions. Regarding oncologists' perceptions of COI that require disclosure, direct financial benefits, such as honoraria, ranked highest (58.5%), followed by gifts from pharmaceutical representatives (50%) and travel grants for attending conferences (44.5%). By contrast, personal or institutional research funding, sample drugs, consulting or advisory board, expert testimony, and food and beverage funded by pharmaceutical industry were less frequently considered as COI. Moreover, only 24% of surveyed oncologists could correctly categorize all situations representing a COI. CONCLUSION: These findings underscore the importance of clear guidelines, education, and transparency in reporting COI in oncology. This hypothesis-generating pilot survey provided the rationale for ONCOTRUST-2 study, which will compare perceptions of COI among oncologists in LMICs and HICs.

The every woman study™ low- and middle-income countries edition protocol: A multi-country observational study to assess opportunities and challenges to improving survival and quality of life for women with ovarian cancer.

BACKGROUND: Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap. METHODS: This is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70-96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women's knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team. CONCLUSION: This study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.

What does it take to conduct clinical trials in African countries? Insights from Morocco.

The progress on cancer diagnosis and treatment has attained, in the last decade, enormous achievements by any estimate. Immunotherapy, new generations of targeted therapies, Chimeric antigen T-cells, cancer vaccines and the fascinating breakthroughs in translational research and cancer biology have changed the direction of cancer care. However, the fact that all patients worldwide cannot have access to these advances is dramatic. Alongside this, taking part in clinical research is one way to improve and invest in cancer care. Patients from African-and most low-resources countries-are rarely offered the chance of being included in clinical trials. This well-known fact paints a disheartening picture of what having cancer is like in the poorest settings. This situation will further decline with population aging, major changes in risk profile imported from developed countries and life expectancy increasing in most African countries. If no radical changes are made, this North-South contrast will become more critical and continue to grow. Yet, there is room for hope because only when we acknowledge the problem can we begin to address it. We need a better understanding of the reasons behind this gap and to advocate for more representation from African patients in clinical trials, with respect to the socio-economic, epidemiological and unique demands of each country across the continent.

Incidence Trends of Cancer in Morocco: The Tale of the Oncological Center of Marrakech (Morocco) over 8 Years.

Background: Determining cancer incidence and mortality is a key factor in the implementation of health policies and cancer prevention strategies. This report aims to describe the trends of cancer incidence in a single referral oncology department from the Marrakech region (Morocco). Material and Methods. All new cancer cases of age ≥ 15 years registered at the Medical Oncology department of Mohammed VI University Hospital of Marrakesh between January 1, 2012, and December 31, 2019, were included. Central nervous system (CNS) cancers, tumors of hematopoietic and lymphoid tissues, and thyroid cancers for which chemotherapy was not indicated or was managed in other cancer-specialized departments were excluded from the analysis. Manual data collection from printed archived medical records of the study population was performed. Descriptive statistics were analyzed using R software and Joinpoint Regression Program. Results: A total of 15648 new cancer cases were analyzed. Missing data (n = 1822) accounted for 11.64%, and 4.1% (n = 652) were excluded. The final statistical analysis and registration included 13174 cases. The median age at diagnosis is 54 years for females and 61 years for males. Female patients outnumbered males with a ratio of 1.58 among all age groups except those aged ≥75 y. The age-standardized incidence rate (ASIR) for all sites was 68,0 per 100.000 person-years, which has increased with an annual percent change (APC) of 10.61%. The five most common malignancies among males are lung, stomach, prostate, colic, and rectal cancers. Among females, the five most frequent cancers are breast, cervix, ovary, colon, and stomach. Conclusion: The higher incidence observed in our results translates into a growing burden on the center and is expected to impact our ability to deliver cancer care. Epidemiological studies to identify risk factors and effective efforts are needed to further invest in cancer control and prevention plans.

Managing cancer care during the COVID-19 pandemic: brief report from a North African single center.

The potential threat of COVID-19 pandemic on the continuity of care for cancer patients is thought to be significant. Oncologists are weighing up the balance of risks and benefits carefully when planning daily cancer care and making treatment decisions in the face of rapid change during this public health crisis. This report describes management strategies and care models that have been adopted by a single Medical Oncology department in a North Africa, Morocco.