Durvalumab for Advanced Rare Tumours

There were no features common to all rare tumours. Advanced slow-growing tumours were more likely to occur in the head and neck region, and metastasis to bone is more likely in patients with cancers arising in the head and neck region compared with primary tumours.

The incidence of these rare tumours in the US is relatively stable, with a mean of 2.45 new diagnoses per 100,000 population per year between 2004 and 2015. Over this time period, the most common rare tumours were Merkel cell carcinoma and malignant peripheral nerve sheath tumour. Over the same period, the incidence of cholangiocarcinoma, peritoneal cancer, and multiple endocrine neoplasia type1 was stable.

Patients with ATN have very good 10 year survival, and some might be curable. There is no prognostic factor that would permit to predict whether a patient might be curable.

Advances in the study of rare cancers are encouraging, but the next challenge will likely include clinical research in the development of novel and effective therapies.

There tends to be poor adherence to clinical trials of new agents and the number is small in comparison with drugs for common cancers. This may have some impact on the quality of evidence available for advanced rare tumours. There appears also to be a discrepancy between reported prescribing patterns and the extent to which patients are benefiting from their treatment. Future studies will require more explicit standardisation of patient selection, inclusion criteria and study design to optimize outcomes in a more explicit and robust manner.

The causes of AROT remain poorly understood and the vast majority will be treated as rare tumour syndromes. As a group of patients with rare tumours, the prognosis is poor, but some patients (especially those with rare tumours presenting early) have a better outcome than patients with rare tumours presenting later. A multidisciplinary approach is required to provide an effective treatment.

As of this time, no such reports involving such disease have been reported. Based upon these observations and current knowledge of the cause, it would be most prudent to recommend that, while the parents and family are examined, genetic testing should be considered. Genetic testing should be offered at the latest to all individuals with advanced rare tumours in a family. However, this can be challenging due to the number of possible mutations, and to reach a diagnosis, it should be done with a specialized team of clinicians.

Clinical trials should be offered to patients who will benefit from clinical treatment and are willing to participate, with particular emphasis on patients who are young or elderly, oncological patients with poor performance status, or in the context of palliative care.

Advanced rare tumours can involve multiple sites; metastases from the lung, brain or bone. In addition, advanced rare tumours can have debilitating effects on individual patients, which should be kept in mind when making management decisions. Advanced rare tumours have been almost uniformly poor prognostic indicators, except for brain metastases.

This phase 3 study shows that patients receiving 200 mg/m³ of durvalumab had a significantly longer progression-free survival compared to patients receiving placebo in addition to standard of care chemotherapy for patients with mCLL. Additional randomized controlled trials of durvalumab in combination with anticancer chemotherapies for patients with the previously described subtypes of mCLL are warranted to determine if this treatment strategy should be incorporated into practice to improve outcomes.

While the short-term QoL improvement observed with durvalumab therapy suggests that a longer follow-up period may prove that sustained benefit may be observed, the QoL questionnaire was poorly suited to evaluate QoL improvement. It appears that no QoL benefit was sustained during long-term therapy with durvalumab. Identifying the relevant patient domains and QoL improvement will be key during future studies.