|LETTER TO EDITOR
|Year : 2021 | Volume
| Issue : 3 | Page : 594-595
A perfect biomarker for immune checkpoint inhibition - An elusive goal?
Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
|Date of Submission||16-Aug-2021|
|Date of Decision||25-Aug-2021|
|Date of Acceptance||30-Aug-2021|
|Date of Web Publication||08-Oct-2021|
Flat 103, Don October Building, Eknath Ghadi Marg, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kumar S. A perfect biomarker for immune checkpoint inhibition - An elusive goal?. Cancer Res Stat Treat 2021;4:594-5
The advent of immune checkpoint inhibition (ICPi) has ushered in a new era of cancer immunotherapy. A recent study from the US has indicated that the percentage of patients who are eligible for ICPi increased from 1.54% in 2011 to 43.63% in 2018. However, the corresponding increase in response rates has been more modest (0.14% in 2011 to 12.46% in 2018). The efficacy of ICPi remains limited as the majority of patients who receive it do not have an adequate response to it. Hence, it is paramount to identify and utilize biomarkers to predict which patients will have an initial and long-term durable response, thereby improving the cost-effectiveness of this new therapeutic modality.
Currently, the FDA-approved biomarkers for ICPi use include programmed death ligand 1 (PD-L1) expression via immunohistochemistry and the tumor mutational burden. PD-L1 expression is the most widely studied biomarker in this field, but it has several limitations. Pembrolizumab approval for the treatment-naïve non-small-cell lung carcinoma was based on the landmark KEYNOTE-024 trial requiring a PD-L1 tumor proportion score (TPS) of ≥50%; however, the response rate to therapy in the experimental arm was only 44.8%, indicating that more than half the patients still do not respond to therapy. Similarly, the approval of pembrolizumab in treatment-naïve advanced recurrent/metastatic head and neck carcinomas was based on the KEYNOTE-048 trial, in which pembrolizumab monotherapy could achieve a response rate of only 23% in the PD-L1 combined positive score (CPS) >20 population. These examples clearly highlight that PD-L1 is an imperfect biomarker and much more work needs to be done in this regard.
It has been postulated that the patient's sex can also play a role in determining the response to ICPi. In this regard, a prior meta-analysis by Conforti et al. showed that men derived greater benefits from ICPi than women (hazard ratio, 0.72 [95% confidence interval (CI), 0.65–0.79] vs. 0.86 [95% CI, 0.79–0.93]; P = 0.002). However, a more recent and robustly conducted meta-analysis has demonstrated no difference in overall survival from ICPi when comparing the two sexes. In this regard, a recent single-center retrospective audit by Kapoor et al., of 155 patients also reached a similar conclusion, showing an equal efficacy and toxicity of ICPi in both male and female patients. This study lacked the statistical power to detect any significant difference between the two sexes as it included a heterogeneous patient population and female patients comprised only 23.2% of the total cohort which compromised the very outcomes that the study intended to analyze.
It is my personal opinion that the quest for the ideal biomarker of ICPi is not an easy one, but one that will only be achieved through a combination of translational studies and future biomarker-guided randomized trials.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Haslam A, Prasad V. Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw Open 2019;2:e192535.
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al.
Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823-33.
Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G Jr., et al.
Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study. Lancet 2019;394:1915-28.
Conforti F, Pala L, Bagnardi V, De Pas T, Martinetti M, Viale G, et al.
Cancer immunotherapy efficacy and patients' sex: A systematic review and meta-analysis. Lancet Oncol 2018;19:737-46.
Wallis CJ, Butaney M, Satkunasivam R, Freedland SJ, Patel SP, Hamid O, et al.
Association of patient sex with efficacy of immune checkpoint inhibitors and overall survival in advanced cancers: A systematic review and meta-analysis. JAMA Oncol 2019;5:529-36.
Kapoor A, Noronha V, Patil VM, Joshi A, Menon N, Mahajan A, et al.
Impact of sex of the patient on efficacy and safety of cancer immunotherapy: A retrospective audit. Cancer Res Stat Treat 2021;4:238-43. [Full text]
Khaddar S, Mishra BK. Biomarkers for response to immune checkpoint inhibitors: Where do we stand? Cancer Res Stat Treat 2021;4:363-4. [Full text]