Perioperative chemotherapy is the standard of care for localized gastric cancer (GC). In 2018, additional postoperative radiotherapy was found to be ineffective; although, docetaxel was found to be superior to epirubicin in perioperative three-drug chemotherapy regimens. Validated biomarkers are needed for benefit from immunotherapy in advanced-stage GC. Metachronous GC can be prevented by Helicobacter pylori eradication.
Key Advances in Clinical Oncology
The Key Advances in Clinical Oncology collection offers a unique series of specially commissioned ‘Year in Review’ articles that highlight the key discoveries made each year. In these articles, leading experts in the field describe their pick of the top 3–5 key advances of the year, outlining their clinical impact and implications for current and future research.
In 2018, the results of multiple phase III trials in metastatic renal cell carcinoma (mRCC) were presented. A phase III noninferiority trial demonstrated the importance of careful patient selection before cytoreductive nephrectomy. Additionally, three randomized phase III trials demonstrated the superiority of combination therapy with an immune-checkpoint inhibitor backbone versus sunitinib in patients with treatment-naive mRCC.
In 2018, several trials in breast cancer have shown efficacy of strategies that rely on novel markers, including gene expression assays or pathological complete response. The relevance of targeted strategies in patient subgroups and of immunotherapy efficacy were demonstrated.
In 2018, advances in the treatment of non-small-cell lung cancer (NSCLC) have been observed both in trials of immunotherapies and targeted agents, leading to dramatically improved options for patients with metastatic and stage III NSCLC.
In 2018, the acute myeloid leukaemia treatment landscape expanded notably, with several trials leading to the approval of novel targeted therapies. Furthermore, comprehensive sequencing revealed the effects of co-occurring mutations and gene expression patterns on drug sensitivity, providing hope that future treatments will be increasingly precise and personalized.
Breakthrough findings reported in 2018 provide the foundations for paradigm shifts in the care of patients with ovarian cancer. These results have implications for treatment in the first-line setting (with improved and refined use of established treatment modalities), firmly introduce concepts of consolidation and maintenance therapy, and enable more accurate prediction of drug sensitivity and resistance.
In 2017, three groundbreaking immunotherapies for relapsed and/or refractory B-cell acute lymphoblastic leukaemia (ALL) were approved based on impressive outcomes observed in clinical trials. Additional breakthroughs included seminal research into ALL genomics and the importance of adherence to chemotherapy, which will have direct implications for clinical care.
In 2017, major advances in the treatment of non-small-cell lung cancer (NSCLC) continued to emanate from the fields of molecularly targeted therapy and immunotherapy. In the former, new drugs with improved efficacy and reduced toxicity entered the clinic; in the latter, immune-checkpoint inhibition proved efficacious after chemoradiotherapy for stage III disease, but had disparate results in the frontline treatment of stage IV disease.
2017 saw the publication of clinical trial data and the approval of new treatment approaches for metastatic urothelial carcinoma. Pembrolizumab is now a well-established treatment for patients with disease progression after cisplatin, with high-level evidence supporting its superiority over second-line chemotherapy. For patients ineligible for cisplatin, atezolizumab and pembrolizumab provide meaningful clinical benefit as frontline therapies.
In 2017, results from phase III trials demonstrated the impressive safety and efficacy of adjuvant targeted and immune therapies in patients with resectable stage III–IV melanoma, and raised questions about the surgical management of patients with microscopic sentinel-lymph-node metastases. For patients with unresectable disease, new overall survival data added to the debate about the relative benefits of single-agent anti-PD-1 versus combined anti-PD-1 and anti-CTLA-4 immunotherapy.
2017 has been full of new discoveries that will influence the treatment of colorectal cancer. In the adjuvant setting, 3 months of chemotherapy might now be considered a new standard of care. Various other new treatments and promising biomarkers have also become available that will improve survival outcomes and the quality of life of many patients with metastatic disease.
Data published in 2017 underscore the benefit of optimizing anti-HER2 therapy in early stage high-risk HER2-positive disease, and of capecitabine in patients with residual disease after optimal neoadjuvant therapy. In the advanced-stage setting, endocrine therapy combined with cyclin-dependent kinase 4/6 inhibitors, or olaparib could become the preferred option.
Data obtained in the past year underscored the benefit of a triplet regimen comprising bortezomib, lenalidomide, and dexamethasone for patients with newly-diagnosed multiple myeloma, and have provided high-level evidence supporting the safety of adding daratumumab to standard-of-care doublets for those with relapsed and/or refractory disease. As a result, achieving minimal residual disease-negativity at any stage of myeloma is now a realistic possibility.
In 2016, the pace of biological insights into small-cell lung cancer (SCLC) was reflected in new treatment approaches that have suggested meaningful clinical benefit to patients. We focus on three highlights of 2016: preclinical studies defining NFIB as a putative driver of metastasis, and two clinical studies; one that assessed the efficacy of an agent targeting the Notch ligand DLL3, and the other that explored T-cell checkpoint-blockade therapies targeting PD-1 and CTLA-4.
In the past year, clinical trials have provided important information on strategies to decrease treatment-associated toxicities in patients with head and neck cancer. In addition, the FDA approved the first immunotherapeutic agents for patients with recurrent and/or metastatic disease, based on the observation of durable responses to pembrolizumab in a phase Ib trial, and demonstration of improved survival and quality of life with the use of nivolumab versus chemotherapy in a phase III trial.
In 2016, novel findings on the role of predisposing gene variants in sarcoma oncogenesis were published, as well as studies addressing novel molecular classifications and results from randomized controlled trials highlighting successful new treatments. Herein, we discuss these meaningful advances.
In 2016, results of an extensive trial broadened the range of malignancies that can be treated with everolimus to include neuroendocrine tumours (NETs) of the lung and gastrointestinal tract. Furthermore, studies aimed at identifying biomarkers with increased specificity, and at better defining high-grade NETs have enabled substantial progress towards delivering effective targeted treatments to patients with NETs.
In 2016, two major trials provided conflicting evidence regarding the role of 1 year of adjuvant therapy with sunitinib for patients with high-risk renal-cell carcinoma. In the second-line metastatic setting, updated data from key trials showed that cabozantinib improved overall survival over everolimus, and nivolumab was associated with a better quality of life compared with everolimus. Finally, a phase II study in previously untreated patients showed cabozantinib to be superior to sunitinib.