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Yi-Long Wu, MD Professor
People's Hospital of Guangzhou Province
President, Lung Cancer Research Institute of Guangzhou
Source: Oncology Frontier(肿瘤瞭望)
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During the heat of China oncology Media covering ASCO(American Society of Clinical Oncology), May 28-June 3, 2015, Chicago, there was a voice appears to be listened the most by Chinese oncologists.
It should not be that much a surprise, as lung cancer is the No 1 killer in both female and male, ASCO is the most covered oncology event, and Yi-Long Wu, MD, Professor, People's Hospital of Guandong Province, is one of the leading figures in China lung cancer research, and he happens to be present President of CSCO (Chinese Society of Clinical Oncology).
Here are some excerpt of his interview commentaries, sometimes serious, sometimes with little humor, by different media regarding some hot topics at ASCO 2015.
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| ASCO 2015 McCormick Place, Chicago Photo:Oncology Frontier |
The Battle for EGFR Drug Tolerance
The drug tolerance problem in EGFR target therapy is a headache to clinicians. CO-1686 (rociletinib abstract 8001)in 2013 and AZD9291(abstract 8000) in 2014 were invented to be the solution, and competing with each other at ESMO and ASCO in the last two years. Each of them has clinical trial paper published in NEJM this April.
So, what's the difference?
At ASCO15, AZD9291 presents with 97 Disease Control Rate(DCR), good median PFS and more than 9 months OS, aiming for first line treatment; CO1686 presents with blood test for tumor cells to detect drug tolerance, suggests it's better than tissue biopsy, which might have limited value. It seemed that each has move one step forward, the game is still on.
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| ASCO 2015 meeting May 29-June 2, 2015 Photo: Oncology Frontier |
More choices for EGFR drug tolerance are coming
There are HM61713 from South Korea, ASP8273 from Japan and EGF816 from Novartis are joining this field.
New agent for brain metastasis
Alectinib(abstract 8008), a second generation of ALK inhibitor, not only is effective in crizotinib tolerance cases, but also shows efficacy for patients with brain metastasis.
Abstract 8016 focus on how to deliver drug to brain more efficiently.
It seems very quite in China. CO1686 focuses most at US and European countries, only AZD9291 is actively involved in China market and working to get final approval from Chinese Food and Drug Administration(CFDA).
However, there will be a novel T790M inhibitor-Avitinib made in China to stop AZD9291's possible future monopoly.
At ASCO15, young and promising French Professor Soria presented LUX-Lung 8 clinical trial outcome on Erlotinib vs. Afatinib, a second generation EGFR target drug.
This is a large clinical trial, enrolled about 800 patients. The result shows that median PFS is 1.9 month vs. 2.6 month, Overall Survival(OS) is 6.8 month to 7.9 month, respectively, which are statistically significant.
However, It is a pure mathematical game. I personally doubt its' clinical significance.
10 years ago, in BR.21 trial, Erlotinib vs. placebo, PFS was 2.2 month vs. 1.8 month; OS was 6.7 month vs. 4.7 month, while there was no competition, and not understanding EGFR mutation's relationship with EGFR inhibitor at that time, Erlotinib was written in second and third lines treatment for Squamous cell lung cancer types in NCCN guidelines.
Three clinical trials in 2013 on EGFR-wild type adenocarcinoma cell lung cancer have basically denied target therapy use.
Recently, ASCO clearly suggested not to use target therapy in EGFR mutation negative patients.
At ASCO15 commentary session, Dr. Gregory Riley at Memorial Sloan Kettering Cancer Center spoke very frankly:" I won't use EGFR inhibitor on squamous cell lung cancer anyway."
He also said, "Please, stop using Erlotinib as a control drug in the EGFR mutation wild type and squamous cell lung cancer clinical trials ."
Target therapy should be put on targeted indication, this also apply to “Hot" Immunotherapy check-point inhibitors.
PD-L1 positive patients' survival could reach 17-18 months, while PD-L1 negative's survival same as chemotherapy. Will PD-1 positive or not determine PD-1/PD-L1 treatment indication? Further clinical trials should be done. We will have to wait and see.
C-MET could be an acquired drug resistance biomarker in NSCLC.
C-MET inhibitor, in combination with EGFR TKI, works well to overcome drug tolerance, yet no effect against c-MET/T790M patients. The mechnism could be through activation of MET and EGFR signal pathway. Abstract 8091 .
In the last 10 years, in some time, China almost took the lead in small molecule TKI anti tumor novel drug development.
9 large clinical trials, almost half were from China. We have done leading work in drug tolerance and translational research.
In the same year, China FDA approved ourselves' ALK inhibitor anti tumor novel drug after U.S. FDA.
We are left far behind in Immunotherapy, at least 5 years left behind. Mature products already have been launched in the world, and we have almost nothing. We should think it over why we did well before(in small molecule target therapy), and failed in Immunotherapy recently.
References:
1.【ASCO 2015】吴一龙教授：学会有选择地改变临床实践 中国医学论坛报今日肿瘤 June 3, 2015 WeChat
2. 【ASCO 2015】吴一龙教授肺癌靶向治疗随想；中国医学论坛报今日肿瘤 June 05, 2015, WeChat
3. 丁香园专访吴一龙教授，June 2， 2015， 肿瘤时间 Video Wechat
4. ASCO[我在现场]吴一龙教授：2015 ASCO会议上的中国声音；肿瘤瞭望, June 01, 2015 Video WeChat
5. Lanying Gou et al. Targeting c-Met overexpression for overcoming acquired resistance to EGFR TKIs in NSCLC, J Clin Oncol 33, 2015 (suppl; abstr 8091)
What's happening in China?
It seems very quite in China. CO1686 focuses most at US and European countries, only AZD9291 is actively involved in China market and working to get final approval from Chinese Food and Drug Administration(CFDA).
However, there will be a novel T790M inhibitor-Avitinib made in China to stop AZD9291's possible future monopoly.
 |
| Millennium Park, Chicago Photo: Oncology Frontier |
Target or Not Target
LUX-Lung 8 result is just a number game
At ASCO15, young and promising French Professor Soria presented LUX-Lung 8 clinical trial outcome on Erlotinib vs. Afatinib, a second generation EGFR target drug.
This is a large clinical trial, enrolled about 800 patients. The result shows that median PFS is 1.9 month vs. 2.6 month, Overall Survival(OS) is 6.8 month to 7.9 month, respectively, which are statistically significant.
However, It is a pure mathematical game. I personally doubt its' clinical significance.
Erlotinib on all lung cancer types treatment guidelines belongs to history
10 years ago, in BR.21 trial, Erlotinib vs. placebo, PFS was 2.2 month vs. 1.8 month; OS was 6.7 month vs. 4.7 month, while there was no competition, and not understanding EGFR mutation's relationship with EGFR inhibitor at that time, Erlotinib was written in second and third lines treatment for Squamous cell lung cancer types in NCCN guidelines.
 |
| ASCO 2015 poster session Photo: Oncology Frontier |
Squamous Cell Lung Cancer should not be on Target Therapy
Three clinical trials in 2013 on EGFR-wild type adenocarcinoma cell lung cancer have basically denied target therapy use.
Recently, ASCO clearly suggested not to use target therapy in EGFR mutation negative patients.
At ASCO15 commentary session, Dr. Gregory Riley at Memorial Sloan Kettering Cancer Center spoke very frankly:" I won't use EGFR inhibitor on squamous cell lung cancer anyway."
He also said, "Please, stop using Erlotinib as a control drug in the EGFR mutation wild type and squamous cell lung cancer clinical trials ."
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| Harold Washington Library, Chicago |
Anti PD1/PDL1 Immunotherapy
Target therapy should be put on targeted indication, this also apply to “Hot" Immunotherapy check-point inhibitors.
PD-L1 positive patients' survival could reach 17-18 months, while PD-L1 negative's survival same as chemotherapy. Will PD-1 positive or not determine PD-1/PD-L1 treatment indication? Further clinical trials should be done. We will have to wait and see.
C-MET overepression
C-MET inhibitor, in combination with EGFR TKI, works well to overcome drug tolerance, yet no effect against c-MET/T790M patients. The mechnism could be through activation of MET and EGFR signal pathway. Abstract 8091 .
China Did Well in TKI-ALK Novel Drug , At Least 5 years Behind in Immunotherapy
In the last 10 years, in some time, China almost took the lead in small molecule TKI anti tumor novel drug development.
9 large clinical trials, almost half were from China. We have done leading work in drug tolerance and translational research.
In the same year, China FDA approved ourselves' ALK inhibitor anti tumor novel drug after U.S. FDA.
We are left far behind in Immunotherapy, at least 5 years left behind. Mature products already have been launched in the world, and we have almost nothing. We should think it over why we did well before(in small molecule target therapy), and failed in Immunotherapy recently.
References:
1.【ASCO 2015】吴一龙教授：学会有选择地改变临床实践 中国医学论坛报今日肿瘤 June 3, 2015 WeChat
2. 【ASCO 2015】吴一龙教授肺癌靶向治疗随想；中国医学论坛报今日肿瘤 June 05, 2015, WeChat
3. 丁香园专访吴一龙教授，June 2， 2015， 肿瘤时间 Video Wechat
4. ASCO[我在现场]吴一龙教授：2015 ASCO会议上的中国声音；肿瘤瞭望, June 01, 2015 Video WeChat
5. Lanying Gou et al. Targeting c-Met overexpression for overcoming acquired resistance to EGFR TKIs in NSCLC, J Clin Oncol 33, 2015 (suppl; abstr 8091)
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