Advanced RET-rearranged NSCLC

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Published: 6 Jun 2016
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Dr Takashi Seto and Dr Kiyotaka Yoh

Dr Seto (National Kyushu Cancer Center, Kyushu, Japan) and Dr Yoh (National Cancer Center Hospital East, Kashiwa, Japan) talk to ecancertv at ASCO 2016 about RET fusions, known oncogenes from a small subset of non-small cell lung cancer  (NSCLC).

Out of 196 institutions in Japan (LC-SCRUM-Japan), 17 RET-rearranged patients who had previously failed to respond to chemotherapy were given vandetanib, a TKI with RET kinase activity.

Dr Seto and Dr Yoh report that vandetanib increased anti-tumour activity, progression free survival and and partial response rates, especially among those from the CCDC6-RET subtype.

ecancer's filming at ASCO 2016 has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.


ASCO 2016

Advaned RET-rearranged NSCLC

Dr Takashi Seto – National Kyushu Cancer Center, Kyushu, Japan
Dr Kiyotaka Yoh – National Cancer Center Hospital East, Kashiwa, Japan

TS: We found a rare mutation of RET by multiplex and FISH and then tried a phase II trial of vandetanib.

What kind of patients were you workig with?

TS: Lung cancer, adenocarcinoma. Enrolled patients were 19 patients however eligible cancer patients were 17.

Were there any markers for the patients?

TS: Screened by multiplex PCR and confirmed by FISH the rearrangement.

Were they EGFR positive or negative tumours?

KY: Our study is in EGFR negative patients in screening.

TS: We used LC-SCRUM, nationwide gene analysis system of LC-SCRUM, so found by LC-SCRUM and enrolled on this study.

Can you tell us more about the patient sub-type?

TS: CCDC6 and T5B [?] RET; we found ten T5B RET and six CCDC6 so the response rate was quite different between the two subtypes. So the response rate of CCDC6 is 83% compared to T5B RET was 20%.

Were there any toxicities associated with the treatment?

TS: Usually the common toxicity with vandetanib, not especially for this study.

Will you use these results in future trials?

KY: RET patients are a very rare population so a phase III trial for RET positive patients is difficult. Our study is a small number of patients, however, our result is consistent with preclinical studies and both with RET positive adenocarcinoma essentially. So our study defines RET rearrangement is a new molecular subgroup of non-small cell lung cancer suitable for targeted therapy.

TS: And LC-SCRUM, now LC-SCRUM using next generation sequencer to detect rare mutations so the next trial in Japan based on LC-SCRUM and now we’ve found the RET so move on to an alectinib trial.