Because, as we know that IIIA-N2 non-small cell lung cancer is a highly heterogeneous disease with different factors of N2 and satisfy outcome. Robinson classified IIIA-N2 into IIIA1 to IIIA4 and this needs a multimodality survey for the N2 patients including the concurrent chemoradiation and surgery followed by adjuvant chemotherapy, neoadjuvant therapy and then surgery and the CTONG trial is encountered in this field. Because the EGFR TKI has been used in the advanced non-small cell lung cancer and moved forward to the maybe adjuvant therapy, therefore we carried out the CTONG 1103 emerging trial in 2011 to enrol the patients with N2 disease also with the EGFR mutation to be randomised into two groups. One is the erlotinib EGFR TKI, the other group is the gemcitabine cisplatin. The primary endpoint of this study is the objective response rate and the secondary endpoints include progression free survival and surgical outcome, including complete resection and lymph node down-staging, the pCR, the pathologic complete remission, and major pathologic question and so on.

Then when it comes to the results have any of the endpoints been met so far?

The endpoint is erlotinib improved objective response rates but the p-value is 0.092, a boundary significant. But the progression free survival of the neoadjuvant erlotinib improved from the gemcitabine group it’s 12 months to the erlotinib group it’s 21 months.

Is there any concern for toxicity between the arms?

The toxicity is mild in the neoadjuvant and adjuvant erlotinib therapy and post-operative complete occasion it’s also very mild, no mortality cases were found in the two groups, consistent with the other study.

Is there any effect of any other therapies before or after?

All the patients are treatment naïve. After the patient relapses the patient will crossover some part of erlotinib to receive the chemotherapy or the chemotherapy group transfer to the erlotinib group.

Can I just double-check, how many patients were involved in the trial?

Totally there are 386 patients were screened and finally 72 patients were randomised and one patient withdrew consent. 72 in the ITT population and 71 in the safety analysis population.

With these lessons, the PFS going from 12 months to 21 months, these sound significant.

The progression free survival is significant and also as we go on with the follow up maybe there will be some update about the progression free survival and the OS data.

What is the timeline for follow up – two years, five years?

The timeline for follow up is every three months. After the surgery every three months we will perform the checks and a normal CT scan and every half year the brain enhanced MRI and every one year have the bone scan.

That covers some of the outcomes, what would you say is the take home message? What is the main lesson from these results?

First of all in stage IIIA-N2 pre-operating staging, stage IIIA-N2 patients with the EGFR mutation I think that erlotinib is the choice to improve the objective response rate and complete resection and down-staging rate and prolong the progression free survival. But it is just a phase II study, we will perform the concept and confirm with the phase III study.

We look forward to more results from the phase III study when they are available.

The study in the neoadjuvant setting of stage IIIA-N2 is very hard to enrol actually. Maybe the later may be transferred to the anti-PD-L1 immunotherapy, it’s also another idea.

So a very active space for research.

OK. From this study we can study the neoadjuvant EGFR TKI, in neoadjuvant anti-PD-L1 the mechanism is somehow different. In the T-cell sample, in the surgical T-cell sample we collected we found that after the neoadjuvant erlotinib therapy the size of tumour cells has decreased and some infiltrating lymphocytes gather around the tumour.
We’ve heard lots of research suggesting tumour infiltrating lymphocytes as the next biomarker to be available.
The biomarker analysis included blood samples and T-cell samples, we have further study later.