Finally there are new developments in small cell lung cancer – can you tell us about radiation therapy in extensive disease?
This is indeed a new concept; it hasn’t been discussed for long. Thoracic radiotherapy was proven in a meta-analysis to be beneficial in limited disease small cell lung cancer and it’s a standard now, and there has been a debate whether the same effect might be achieved in extensive disease. Despite dissemination of the tumour, thoracic disease is still the largest mass in small cell lung cancer so there were some arguments to consider it. And the Dutch group performed a very interesting randomised study investigating this concept comparing standard therapy, which is systemic therapy alone with cranial radiation, versus the same with the addition of thoracic radiation and surprisingly there is some benefit from thoracic radiotherapy. So, of course, this study necessitates a longer follow-up; the benefit was seen only after two years, so the curves diverged after 12 months, but this is an important message. We should consider it again as important progress in this category of patients which have particularly poor prognosis.
Is there a question mark over prophylactic cranial irradiation?
This is a little bit of a surprise, a Korean study showed that there is no benefit of cranial radiation, prophylactic cranial radiation, in extensive disease small cell lung cancer which is in contradiction with the previous Slotman study. By the way, the radiotherapy in extensive disease small cell lung cancer was also presented by Slotman so he’s the guy doing large, important, practice-changing studies in small cell lung cancer. Coming back, prophylactic cranial radiation was shown to provide no benefit in terms of overall survival, the study was stopped due to futility analysis. So the question now is how to treat these patients because we have one clearly positive study and one clearly negative study and the difference is probably that we have now more diagnostic tools. All these studies in the Korean study underwent brain MRI before entering into the study so some asymptomatic brain metastases were found, this was not the case in the previous study. Maybe there are some other differences, it’s a different population of patients, there might be some ethnic factors. But the message is here so we have to consider this study seriously.
And we are finally seeing new medicines for cell lung cancer?
Yes, there has been no new drug for decades in small cell lung cancer. The study that was presented here showed that standard second line therapy with teniposide is probably less effective than a triplet including two standard drugs, this is teniposide, cisplatin in addition and the third drug is irinotecan. Irinotecan has been tested in several studies in small cell lung cancer and some of the studies showed some benefit but it still has not been considered as standard. Here we see that there is an important difference, important benefit, of using triplet rather than single agent teniposide in second line therapy. So, again, this might change the practice.
What about non-small cell lung cancer and chemotherapy?
Yes, consolidation chemotherapy after chemo-radiation in stage 3 in non-small cell lung cancer has long been a subject of debate. In this country, in the United States, it was considered until recently a standard. Our American colleagues use docetaxel in consolidation therapy. This strategy was shown to be ineffective and I believe this practice is not continued any more. This new study showed and investigated the effect of doublet, including docetaxel and cisplatin or carboplatin, as the consolidation therapy after chemo-radiation in non-small cell lung cancer and again showed absolutely no benefit. So these patients are really tired after intensive chemo-radiation and they deserve some vacations and it’s good news for them that this very toxic therapy is not necessary in this setting.
Can you tell us about the new drugs for non-small cell lung cancer?
There are many good news for non-small cell lung cancer patients. Non-small cell lung cancer is becoming a mixture of several diseases with various molecular features and EGFR mutated tumours is one category, it’s the largest of those, but also R positive and MET positive tumours and much more, HER2 positive tumours. All these patients will necessitate different molecular therapies, this is obvious because they have different molecular targets. Introducing anti-EGFR therapy was a real breakthrough in EGFR mutated patients, the same was true for R positive patients and crizotinib. Now we have several new compounds that are effective both in first and in second line treatment of both categories of patients. For example, sunitinib was found to be very effective in R positive tumours, both in first and in the second line. We have also several drugs that are effective in EGFR positive tumours, that means that these patients may continue anti-EGFR therapy much longer before they totally relapse and will necessitate chemotherapy or some other therapies. So this is indeed very good news.
How would you summarise the data on lung cancer?
I would say interesting data for lung cancer, both for non-small cell and for small cell. The studies I addressed may change practice. All these studies are potentially practice changing so this is always important. If you consider new data in these categories, they are indeed important.