PRACTICE GUIDELINES

Therapy-orienting testing of EGFR inhibitor-resistant non-small cell lung cancer

SUMMARY

Somatic sensitising mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are detected in approximately 10% of patients with advanced non-squamous non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the first-line treatment option for patients with an actionable EGFR mutation. Despite initial responses, the majority of patients progress within one to two years after EGFR-TKIs treatment initiation.

The most common mechanism of resistance is the development of an additional EGFR-T790M mutation in exon 20, found in 50–60% of EGFR-mutant NSCLC patients who were rebiopsied on EGFR-TKI treatment. Phase II and III trials with osimertinib, a third-generation EGFR-TKI, demonstrated an objective response rate (ORR) of 60–70% and median progression-free survival (mPFS) of 10–11 months in EGFR-T790M-positive tumours.

A tissue biopsy of a progressing lesion for confirmation of histology and molecular characterisation is a critical consideration. However, a repeat tissue biopsy is not possible for every patient. Therefore, a liquid biopsy can be considered for EGFR-T790M mutation testing. Indeed, clinical trials testing osimertinib have shown similar clinical outcomes (ORR and mPFS on osimertinib) in patients with T790M-positive plasma versus T790M-positive tumour tissue.

Osimertinib clearly expands relapse treatment options for advanced stage EGFR-mutant NSCLC. Testing for EGFR-T790M at acquired resistance should become a standard component of patient care in EGFR-mutant tumours. In this manuscript, we propose and discuss two possible clinical diagnostic algorithms that could be used for the therapy-orienting testing of EGFR-TKI-resistant NSCLC patients. Tissue and liquid biopsies involve challenges in terms of specific clinical role, safety, logistics, and cost.

(BELG J MED ONCOL 2017;11(5):226–233)

Radium-223, patient selection is of utmost importance

SUMMARY

In this practice guideline, the use of clinical indicators to increase the chance of completing six cycles of radium-223 in patients with metastatic castration-resistant prostate cancer is discussed.

(BELG J MED ONCOL 2017;11(3):107–109)

Management of non-small cell lung cancer patients EGFR mutated and ALK translocated

SUMMARY

In recent years, considerable advances have been achieved in the treatment of non-small cell lung cancer. The discovery of EGFR mutations and ALK translocations has changed clinical management. However, several mechanisms carrying resistance to EGFR tyrosine kinase inhibitors have been reported, as well as resistance to ALK-targeted drugs.

In this review we will focus on non-small cell lung cancer patients with EGFR mutations and ALK translocations, providing a suggested therapeutic algorithm for treating these patients.

(BELG J MED ONCOL 2017;11(3):110–121)

The Belgian next generation sequencing guidelines for haematological and solid tumours

SUMMARY

Targeted next generation sequencing is a complex procedure including the ‘wet bench’ and ‘dry bench’ parts. Both parts are composed of many steps for which optimal assay conditions and settings must be determined.

The aim of these guidelines is to provide generic, platform independent, recommendations for targeted next generation sequencing tests to detect acquired somatic mutations in DNA, in (haemato)-oncology that are complementary to the ISO 15189 norm (medical laboratories) in order to:

1. facilitate the implementation of the required quality metrics for the detection of somatic variants by next generation sequencing in oncology and haemato-oncology in the Belgian laboratories,
2. harmonise test validation and verification,
3. harmonise clinical interpretation and reporting of variants and,
4. assure and maintain optimal test performance by establishing procedures and modalities for internal quality control and external quality assessments.

(BELG J MED ONCOL 2017;11(2):56–67)

Guidance for the prevention and treatment of venous thromboembolism in cancer patients

Summary

Venous thrombosis is a common complication in cancer patients and thromboembolism is the second most common cause of death. Several practice guidelines provide recommendations for the management of cancer-associated thrombosis. However, these guidelines do not sufficiently cover commonly encountered clinical challenges. With this expert panel, consisting of medical oncologists, haematologists, internists and thrombosis specialists, we aimed to develop a practical Belgian guidance for adequate prevention and treatment of cancer-associated thrombosis that covered several challenging situations encountered in daily clinic. This paper discusses the following topics: type and treatment duration of anticoagulant therapy, recurrent VTE despite anticoagulation, anticoagulation in case of renal impairment, liver disease and thrombocytopenia, the role of anti-Xa monitoring, central venous catheter-associated thrombosis, the position of direct oral anticoagulants and thromboprophylaxis, both in ambulatory and hospitalised patients. For an overview of the recommendations formulated by the expert panel, we refer to the key messages for clinical practice in this article.

(BELG J MED ONCOL 2016;10(7):249–255)

Therapeutic approaches in clear cell and non-clear cell renal cell carcinoma

Summary

Renal cell carcinoma accounts for 2.4% of all malignancies worldwide diagnosed with 338,000 estimated new cases globally in 2012. In the last decade, the therapeutic landscape for renal cell carcinoma patients has changed tremendously. In this review, we will summarise the treatment options currently available for clear-cell localised, advanced and metastatic renal cell carcinoma; as stated in the ESMO clinical practice guidelines, the EAU guidelines and the NCCN guidelines. Furthermore we will discuss the recommended therapies in patients diagnosed with non-clear cell tumours.

(BELG J MED ONCOL 2016;10(7):256–262)

Recurrent and metastatic non-nasopharyngeal head and neck cancer: state of the art of systemic treatment

Summary

The majority of patients diagnosed with recurrent and/or metastatic squamous cell carcinoma of the head and neck are deemed ineligible for surgery or irradiation. Their management prioritise symptom control and quality-of-life improvement. According to patient’s performance status, medical comorbidities and symptoms, recommended treatment options include supportive care only, mono- or multi-drug chemotherapy or cetuximab (epidermal growth factor receptor inhibitor) either alone or as an adjunct to cytotoxic drugs. Despite achieving response rates superior to single-agents, doublet and triplet regimens incorporating cisplatin and/or taxanes did not increase overall survival and were often difficult to tolerate. The platinum (cisplatin or carboplatin)/5-fluorouracil/cetuximab regimen is the only regimen showing significant survival improvement over PF alone in a large randomised trial, and therefore is the only approved new standard systemic treatment today. However, the very poor overall survival of six to ten months expected in this patient population, remains a continuous challenge and novel anticancer therapies are urgently needed. The potential to induce durable responses with manageable toxicity has propelled immunotherapy to the forefront of cancer research, yet its validation in phase III clinical trials is pending. Another crucial task is the identification of reliable, prospectively confirmed prognostic and predictive biomarkers. Mounting evidence from retrospective analyses suggests that human papillomavirus status with p16 immunohistochemical positivity as its surrogate represent promising candidates for this role.

(BELG J MED ONCOL 2016;10(6):207–214)