O-drug (trade name Opdivo) refers to Nivolumab, manufactured by Bristol-Myers Squibb, which has been approved by the FDA for second-line treatment of advanced NSCLC (squamous and adenocarcinoma).
K drug (trade name Keytruda) refers to Pembrolizumab, manufactured by Merck Sharp & Dohme and approved by the FDA in advanced NSCLC as first-line therapy for PD-L1 expression above 50% and second-line therapy for PD-L1 expression above 1%.
The K drug was approved by the FDA for first-line treatment of patients with advanced NSCLC because it delivered better survival and higher disease remission rates as first-line treatment in the KEYNOTE024 study. However, this is a comparison of K drugs with chemotherapy, not a direct comparison study of K drugs with O drugs, and does not indicate that K drugs are superior to O drugs.
Both O and K drugs can be used as second-line therapy; are they superior or inferior? At this point, the two drugs have not had a chance to get into the ring for a direct comparison (there are no head-to-head prospective controlled studies yet), so we can only compare them in terms of their efficacy, adverse effects, and current price in the approved studies to see how they differ in second-line therapy (see “What are the characteristics of each of the several drugs currently available? question in Table 1).
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Comparing the data in the table shows that there is no significant difference between O and K drugs in terms of disease remission, prolonged survival, and adverse effects in second-line NSCLC treatment. However, in PD-L1>50% of patients, it appears that K drugs are somewhat more effective. However, none of these data are the result of a direct comparison between the two drugs, so they can only be used as a reference. In terms of price, the O drug is slightly cheaper than the K drug, but the difference is minimal.
The CHECKMATE026 study, published at the same time as the KEYNOTE024 study, failed to meet the primary clinical endpoint (PFS) with O in the first line. However, the results of this study may be related to its failure to screen for appropriate patients, and the investigators’ subsequent analysis found that after switching to screening patients with a tumor mutational load (TMB) rather than PD-L1 expression >5%, they were able to better identify a population for which O-drug therapy was effective. Thus, the jury is still out on exactly how effective O drugs are in first-line therapy.
Co-reviewed by: Guangdong Provincial People’s Hospital Guangdong Provincial Lung Cancer Institute Dr. Wang Zhen, deputy chief physician Dr. Kai Yin