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| Jun Guo, MD PhD Professor Dean, Depart of Skin and Kidney Cancer Cancer Hospital of Beijing University Chairman, Melanoma Society, Chinese Society of Clinical Oncology |
LBA1, a breakthrough trial
LBA1 research result unveils at the ASCO 2105. This multicentered, phase III clinical study confirmes that nivolumab (NIVO) + IPI is geater than and NIVO monotherapy in clinical activity to treat melanoma, and two immune targeted drugs have synergy activity.
Although this study is done in melanoma, but the outcome has a universal significance.
More and more breakthrough has been made in Immunotherapy to treat melanoma in recent years. The first breakthrough is CTLA 4 monoclonal antibody Ipi, which prolongs the survival of advanced melanoma patients;
Again, the researchers confirm PD - 1 antibodies' remarkable efficacy after Ipi treatment failed or not received Ipi (Ipi naive) in the patients.
The breakthrough point of the study presented at ASCO 2015 is 1. the PD - 1 inhibitor gets into first-line treatment in advanced melanoma, more effective than CTLA 4 antibody; 2. Ipi in combination with NIVO PD-1 inhibitor, work better than single agent.
This phase Ⅲ clinical study obtained impressive result. The combination regimen is obviously more effective than Ipi alone, having reached 57.6% response rate, PFS 11.5 months, overall survival has not yet been achieved.
In China, chemotherapy is only effective 7% for melanoma patients, and PFS is just 1.4 months.
I am really looking forward to next year's ASCO meeting, hopefully the overall outcome will be available.
I agree with the expert who participated in discussion. According to the existing evidence, doesn't matter it's Nivolumab (NIVO) or Pembrolizumab (Pembro), each should be recommended as the first-line therapy for melanoma.
Ipi as single drug to be used first-line treatment for advanced melanoma might belong to the history.
Patients subgroup analysis necessary
There is no final conclusion by head to head trial with NIVO and Pembro. Both are effective. The combination of Anti PD - 1 with IPI achieves higher response rate and longer PFS, especially for PD - L1 < 5% patients; combination is significantly better than NIVO alone and NIVO is more effective than Ipi.
Based on this result, I personally feel treatment choices will be based on melanoma subgroup in the future. NIVO or Pembro alone is enough for advanced melanoma patients with PD - L1 high expression. Considering the cost of medical, patients can save nearly 1/5 of the cost if on single drug, with almost the same efficacy.
With PD - L1 low expression, the efficacy of the combined group was significantly higher than that single drug groups. So for patients with PD - L1 low expression, combination is promising.
Side effect serious
At ASCO 2015, both trials with Ipi in combination with NIVO in melanoma have serious side effects.
Combination groups are significantly higher than the single drug groups, with 3 ~ 4 levels of side effects reaching 55%. 36.4% of patients discontinued the drugs because of treatment-related side effects.
A couple of notes
Therefore, clinicians should pay attention to ensure the combination regimen efficacy, yet in the same time to reduce the side effect in the future. Maybe to use immunosuppressants or to increase NIVO or Pembro's dosage could be the choice, etc.
The second direction is to find sensitive patients. PD - L1 is still not be the best antibody biomarkers to predict PD - 1 single drug or the combination regimen's efficacy.
Lots of basic research is needed in this aspect. And researchers in China can contribute.
At the same time, these studies' outcome may influence the treatment of other tumors.
Immunotherapy expanded uses
At present, immunotherapy on lung cancer, breast cancer, colorectal cancer, kidney cancer are under way . Some success has been made in the treatment of tumors other than melanoma with CTLA 4 antibody, PD-1 inhibitor etc.
In addition, potential biomarkers need to be discovered , such as CD8 T cells invading the edge of the tumor and PD - L1 expression, T cells clone in the tumor and mutation burden etc.
Conclusion
In conclusion, immunotherapy has become the new paradigm for advanced melanoma.
This study has proved that combination regimen of Nivo with Ipi is superior to Ipi alone, but no biomarkers can be used for proper patient screening.
A new immune inhibitor combination regimen standard of care has been established, but still, there are lots of works needed to be done.
Reference:
郭军【ASCO 2015】独家：郭军教授点评大会报告LBA1 2015-06-02 中国医学论坛报》 微信公众号
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