Clinical Oncology

[Tumor-agnostic therapy in oncology]

UHLYARIK Andrea1,2

DECEMBER 30, 2020

Clinical Oncology - 2020;7(4)

[Tumor-agnostic therapy is considered as a promising therapeutic approach in oncology, however classification, validation of the targets and standardized methodology for their evaluation is mandatory. The development and approval of the tumor-agnostic drugs should be based on biomarker driven clinical trials. To date three validated biomarkers are known, the high microsatellite instability (MSI-H), the fusion of the neurotrophic-receptor-tyrosine-kinase (NTKR) genes, and the high mutation burden (TMB-H) of the tumors. Pembrolizumab (anti-PD-1 antibody) was the first approved tumor-agnostic drug, the MSI-H status of the tumor was the first indication, then later the TMB-H status was also approved. Larotrectinib and entrectinib are approved for the treatment of NTKR fusion-positive tumours.]

AFFILIATIONS

  1. Semmelweis Egyetem, Belgyógyászati és Onkológiai Klinika, Budapest
  2. Szent Borbála Kórház, Tatabánya

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ÁROKSZÁLLÁSI Anita

[Yearly around half a million women are diagnosed with uterine cancer worldwide, having leaded to 90,000 deaths in 2018. Endometrial cancers (ECs) are the most common forms of gynaecological malignancies, while sarcomas represent not more than 3% of uterine cancers. In 80-85% of cases ECs are low-grade and diagnosed at an early stage, therefore potentially curable by surgical procedure and postoperative radiotherapy (if necessary). However, the optimal adjuvant management of high risk ECs is still an issue and the recognition of molecular subtypes is generating further clinical investigations in the field. Surgery is also the only curative method in sarcoma-care, but evidences for adjuvant management is scarce and indefinite. Beyond therapeutic benefits, quality of life is also an important factor in modern oncology. Therefore in gynaecological oncology there are intentions like preserving fertility and ovarian function, avoiding systemic lymphadenectomy or using minimal invasive technique to improve the patients’ quality of life without the deterioration of the therapeutic outcome. In the management of advanced endometrial cancer, the biological agents have opened a new era in recent years: pembrolizumab as second line option for MSI-H/dMMR/TMB high EC and the combination of lenvatinib-pembrolizumab for MSS/pMMR EC have been approved. But there are also promising results or ongoing studies with other agents: anti-HER2 therapy for serous EC, cabozantinib-nivolumab or ipilimumab-nivolumab for carcinosarcoma, PARP inhibitors with endocrine therapy for ER positive ECs. Here I present a short summary on the current therapeutic options and the most important ongoing clinical trials in uterine cancer.]

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[The year of 2020 brought unexpected challenges to the healthcare systems all around the globe. Every country had to reorganise their medical priorities to face the COVID19 pandemic. The practice of virtual medicine has expanded in the past years, these new circumstances have increased its speed drastically. Within these unusual circumstances we could take part in the virtual congress of the ESMO 2020 where we were able to hear about the new results of oncology to provide up-to-date care for our patients. Compared to the past years, we did not learn too many breakthrough results, the most of the novelties helped us place our experiences to their ideal place in patient care. The investigations which examined the SARS-CoV2 virus effects on oncologic patients showed grave results, the infection increases the vulnerability and mortality of patients receiving active anticancer therapies or suffering from an active cancer.]

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[The forefront of ovarian cancer therapy: update on PARP inhibitors]

MIRZA M R, COLEMAN R L, GONZÁLEZ-MARTIN A, MOORE K N, COLOMBO N, RAY-COQUARD I, PIGNATA S

[In recurrent ovarian cancer, poly(ADP-ribose) polymerase (PARP)-inhibiting agents have transformed the treatment of platinum-sensitive disease. New data support use of PARP inhibitors earlier in the treatment algorithm. We review results from recent phase III trials evaluating PARP inhibitors as treatment and/or maintenance therapy for patients with newly diagnosed ovarian cancer. We discuss the efficacy and safety of these agents in the all-comer and biomarker-selected populations studied in clinical trials, and compare the strengths and limitations of the various trial designs. We also consider priorities for future research, with a particular focus on patient selection and future regimens for populations with high unmet need. Four phase III trials (SOLO-1, PAOLA-1/ENGOT-OV25, PRIMA/ENGOT-OV26 and VELIA/GOG-3005) demonstrated remarkable improvements in progression-free survival with PARP inhibitor therapy (olaparib, niraparib or veliparib) for newly diagnosed ovarian cancer. Differences in trial design (treatment and/or maintenance setting; single agent or combination; bevacizumab or no bevacizumab), patient selection (surgical outcome, biomarker eligibility, prognosis) and primary analysis population (intention-to-treat, BRCA mutated or homologous recombination deficiency positive) affect the conclusions that can be drawn from these trials. Overall survival data are pending and there is limited experience regarding long-term safety. PARP inhibitors play a pivotal role in the management of newly diagnosed ovarian cancer, which will affect subsequent treatment choices. Refinement of testing for patient selection and identification of regimens to treat populations that appear to benefit less from PARP inhibitors are a priority.]

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