May 31, 2015, Chicago, Thomas Lynch, MD, Director, Yale
Cancer Center, widely recognized as the pioneer in Lung cancer novel medicine development
and EGFR mutation molecular testing, sits down with Yuan-Kai Shi, MD PhD, Vice
president, Cancer Hospital, Chinese Academy of Medical Science , Beijing, who is one
of the three co-chairs who wrote the new releasaed"The 2015 China Primary Lung Cancer Diagnosis and
Treatment Clinical Practice Guidance", to discuss highlights at ASCO 2015 in non
small cell lung cancer.
 |
| Drs Lynch and Shi's interview by "Oncology Frontier"(China) McCormick Place, Chicago |
Oncology Frontier: Dr Lynch, as a pioneer in the EGFR-mutated cancer field, what progress have we have seen at this 2015 ASCO Annual Meeting?
Dr Lynch: We have had a lot of good examples of progress at this year’s ASCO meeting. We have learned that AZD9291 looks like having excellent activity as first-line treatment in patients with EGFR-mutated lung cancer. We have learned that the Clovis compounds also have activity in T790M-mediated resistant tumors and maybe some patients without T790M mediated resistance.
These two new drugs, in addition to afatinib, icotinib, erlotinib and gefitinib will give doctors more choice. In China, I would imagine the disease is a bigger issue for you than in the United States given how much more common EGFR-related mutations are in China.
Dr Shi: Because of the genetic background, the disease differs between the Caucasian and Oriental populations. For EGFR mutations, patients in the Caucasian population make up about 17%, but from our Chinese multi-center study, we found 50% of our adenocarcinoma patients had the EGFR-active mutation. So I believe the EGFR TKIs will be used more frequently in Chinese adenocarcinoma patients because of the higher incidence of the EGFR-active mutation.
Anti PD-1/PD-L1 new drugs in NSCLC
Dr Lynch: I agree. One thing I was disappointed about here at ASCO was that we had the presentation on the PD-1/PD-L1 study and it didn’t look like the EGFR mutation group seemed to benefit as much as we all might have hoped. We aren’t completely certain of that yet as the numbers are small and more study is needed particularly in Asia.
I think the PD-1 and PD-L1 drugs are very exciting in cancer. In the EGFR setting, I don’t think we know enough yet. Data presented today showed good results with melanoma, but the whole class of drugs is very promising.
Dr Shi: I would like to ask Dr Lynch what his thoughts are on combining EGFR TKIs and PD-1/PD-L1.
Dr Lynch: It’s a great question but we just don’t know yet. There are many ongoing trials now looking at combinations so we will have to wait for that data.
Dr Shi: The PD-1/PD-L1 therapies are developed by Western pharmaceutical companies and we are only beginning clinical study and development in China.
In the future, we will have more experience and data.We are currently doing translational research to determine what percentage of EGFR-mutated patients has PD-1 expression. I don’t have precise data so far but you can expect us to announce our findings later.
I think the PD-1 and PD-L1 drugs are very exciting in cancer. In the EGFR setting, I don’t think we know enough yet. Data presented today showed good results with melanoma, but the whole class of drugs is very promising.
Dr Shi: I would like to ask Dr Lynch what his thoughts are on combining EGFR TKIs and PD-1/PD-L1.
Dr Lynch: It’s a great question but we just don’t know yet. There are many ongoing trials now looking at combinations so we will have to wait for that data.
Dr Shi: The PD-1/PD-L1 therapies are developed by Western pharmaceutical companies and we are only beginning clinical study and development in China.
In the future, we will have more experience and data.We are currently doing translational research to determine what percentage of EGFR-mutated patients has PD-1 expression. I don’t have precise data so far but you can expect us to announce our findings later.
Icotinib is China’s innovative drug for advanced EGFR mutation-positive NSCLC. The ICOGEN study, “Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer: a randomized, double-blind phase 3 non-inferiority trial” was published in Lancet Oncology on 13 August 2013. What is your comment on the efficacy of icotinib and its significance in treating EGFR mutation-positive advanced NSCLC?
Dr Lynch: I have known about icotinib for many years because I got to meet the investigators at the BETA Pharmaceuticals US office in New Haven, Connecticut. I was always impressed by the toxicity profile of icotinib. The data I have seen has always looked very encouraging.
The only downside was it has to be taken three times a day but that may be more tolerable with a reduced side effect profile.
Dr Shi: From the ICOGEN trial here in China, my experience is also is that icotinib has low toxicity compared to other EGFR TKIs. Even though the dosing is three times daily, it is easily tolerated by patients. We also designed the clinical trial as a first-line treatment compared to pemetrexed and cisplatin.After four cycles of induction chemotherapy, we use pemetrexed as maintenance therapy and the results will be announced soon. I am really looking forward to the results for icotinib in the first-line setting. Last year, we received Chinese FDA approval for the use of icotinib as second-line therapy in EGFR-mutated NSCLC.
The only downside was it has to be taken three times a day but that may be more tolerable with a reduced side effect profile.
Dr Shi: From the ICOGEN trial here in China, my experience is also is that icotinib has low toxicity compared to other EGFR TKIs. Even though the dosing is three times daily, it is easily tolerated by patients. We also designed the clinical trial as a first-line treatment compared to pemetrexed and cisplatin.After four cycles of induction chemotherapy, we use pemetrexed as maintenance therapy and the results will be announced soon. I am really looking forward to the results for icotinib in the first-line setting. Last year, we received Chinese FDA approval for the use of icotinib as second-line therapy in EGFR-mutated NSCLC.
Future strategies to improve lung cancer treatment
Dr. Lynch: We are very lucky in the field of lung cancer as there has been so much development over the last ten years. We now have five drugs that are effective in EGFR-mutated lung cancer. We are on the verge of also incorporating immunotherapy.
The challenge for us as doctors is that when doing molecular profiling, do we have enough options to meet a patient’s molecular profile? One place I think we need more help with better clinical trials is with Ras-mutated lung cancer. In the United States, ras makes up about 30% of our adenocarcinomas and we have very few options for treating ras-mutated adenocarcinomas.
The challenge for us as doctors is that when doing molecular profiling, do we have enough options to meet a patient’s molecular profile? One place I think we need more help with better clinical trials is with Ras-mutated lung cancer. In the United States, ras makes up about 30% of our adenocarcinomas and we have very few options for treating ras-mutated adenocarcinomas.
Dr. Shi: In China, the incidence is less in RAS-mutated lung
cancer, but it is certainly the next problem to be solved.
In the recent times, China's pharmaceutical industry has undergone an historic transformation from imitation to innovation. If you look forward, will China evolve into a major force in drug innovation?
Dr Lynch: My opinion is very strong. We have seen tremendous commitment to science and investment in science from China. The commitment I see to genomics and understanding the genetics of cancer, for example, will be of huge benefit to China and the whole of Asia by performing genomic profiling and bringing new drugs to market.
Dr Shi: In recent years, Chinese domestic pharmaceutical companies have made huge efforts to develop drugs; not just generic drugs but also novel agents. There are more and more drugs going to clinical trials and consequently more Chinese doctors contributing to clinical research for anti-cancer therapies and also translational medicine.
Reproduced from Oncology Frontier
Disclosure:
Dr. Lynch is one of the Directors of Board of
BMS; Dr. Shi has been PI for several Bettapharma sponsored clinical trials on
Icotinib.
Reference:
1. [ASCO 巅峰对话] Thomas Lynch教授、石远凯教授现场解读ASCO热点 2015-06-02 肿瘤瞭望
2. Shi YuanKai etc. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. The Lancet Oncology, Volume 14, No. 10, p953–961, September 2013
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