New drugs in thoracic oncology: needs and knowledge – an online ERS Lung Cancer Assembly survey

Discussion

Lung cancer management has evolved from a simple “all-fit-in” strategy based on surgery, radiotherapy and conventional chemotherapy to a complex algorithm concerning specific biological entities (oncogenic driver mutations/inflammatory tumours) and new systemic therapies having specific mechanisms of action and toxicity profiles. This survey, the first milestone of the CRC RATIONALE masterplan, as an essential part of the ERS Thoracic Oncology Assembly, emphasised the need for providing information to lung cancer specialists about national and European legal processes of drug prescription and indications, as well as toxicity descriptions and management in three therapeutic fields: 1) targeted therapies; 2) monoclonal antibodies; and 3) immunotherapies.

Twenty years ago, lung cancer was separated into two distinct entities, small cell lung cancer (SCLC) and NSCLC, with dedicated therapeutic strategies. With the reporting of the first actionable oncogenic driver mutation in 2004 [22], a new era of targeted therapies was opened and other targets were rapidly discovered [23]. While advances were made they only concerned small groups of patients, moving from a common cancer to rare entities so that physicians have limited experience either for diagnosis, treatment or toxicity management. More recently, immunotherapy developments led to the introduction of anti-PD1/PDL1 antibodies into routine care for a very large group of NSCLC patients. However, physicians are now confronted by toxic autoimmune manifestations, an uncommon situation in lung cancer which justifies the assistance of organ-specialists who are in turn not aware of lung cancer specificities. Furthermore, at the difference of conventional chemotherapy and first/second generation EGFR TKI, there are not only very specific toxicities associated with new drugs (e.g. visual disturbances associated with ALK inhibitors) but also differences in the incidences of similar toxic events inside the same class of drugs (less skin reaction and diarrhoea for osimertinib compared to first/second generation EGFR TKIs (gefitinib, erlotinib and afatinib)) or therapeutic approaches (more immune adverse events with ipilimumab compared to anti-PD1). The present survey, mainly representing medical (pneumo)oncologists, underlines some deficits in knowledge amongst lung cancer clinicians in these different domains. The exception is EGFR mutation and TKI, probably because of less complexity than currently noted in the ALK translocated tumours and more than a decade of use in routine practice.

Respondents to this survey clearly supported the development of a user-friendly system providing updated information on toxicity prevalence and description of new systemic drugs in lung oncology. The CRC RATIONALE is building an industry-independent web platform (To“X”csin) where toxic events may be prospectively recorded. Their expectation is also to have the possibility of sharing experience with other specialists not only about lung toxicity but about any organ toxicity. We can question the current way of obtaining such information. There are numerous sources of data coming from the pharmaceutical industry but, without any value judgement in the present situation, these can be biased as was previously reported for psychiatric medications [24]. Furthermore, reporting adverse events to national and European medical agencies is a legal constraint; however, the response via information for the physicians sometimes seems limited or delayed, since regular updates on types and frequencies of adverse events are difficult to obtain and official modification of medical notices (often after substantial documentation of relevant adverse events) may take time due to bureaucratic processes. This emphasises the need for a new up-to-date and rapid communication platform, directed by and designed for the physicians, which will be ensured by the aspired to To“X”csin platform.

Two main questions arise for the survey. The first is regarding the number of participants, as the first call allowed us to obtain around 100 responses and with the second call we increased this number to more than 300. This appears to be a relatively low value according to the number of ERS members; however, it is evident that answers to surveys are generally low, especially amongst physicians of which only a minority are involved in lung cancer treatment and who receive many solicitations. The second question of importance is whether the respondents are representative of the European lung cancer community. Participants covered all the different parts of Europe and the slight male majority is also reflective of the current tendency in gender repartition. Age distribution shows that most respondents are active experienced physicians, although we observed some discrepancy regarding the site of activity with an excess of academics and universitarians. Despite this, the need for information remains important. Most of the respondents were pneumologists and very few were from other specialties. However, in most European countries, pneumologists are in charge of first-line lung cancer diagnosis and treatment.

Facing the evolving complexity in NSCLC management and the rapid introduction of new systemic therapies, the lung cancer community is requesting new information and communication modes for sharing experience with toxicities that are underlined by this online survey. Thus, the CRC RATIONALE within the ERS Thoracic Oncology Assembly has elaborated a website dedicated to this topic. We expect that To”X”csin will be available in 2018, provided that all legal constraints are reached.