A Comprehensive Analysis Clarifies What We Know About the Use of Cisplatin and Carboplatin in Solid Tumors
Two of the most widely used chemotherapy drugs in cancer treatment, cisplatin and carboplatin, have been part of oncology practice for decades. However, the strength of the evidence supporting the choice between them varies considerably depending on the tumor type and the clinical outcome analyzed.
This is the finding of a study published in JAMA Network Open, with the participation of Dr. Judit Sanz, a researcher in the Clinical Oncology group at the Institut de Recerca Sant Pau (IR Sant Pau) and a physician in the Medical Oncology Department at Hospital de Sant Pau, which comprehensively reviewed the efficacy and safety of both treatments. Dr. Sanz contributed to this work during an external rotation in her final year of residency at The Royal Marsden NHS Foundation Trust in London. Although the drugs belong to the same class and act through similar mechanisms, they differ both in their efficacy in certain diseases and in their adverse effects, meaning that choosing one over the other can have important implications for each patient.
“Cisplatin and carboplatin are treatments we have used for many years, and there is an enormous body of scientific literature on them. However, having many studies does not necessarily mean we have the same degree of certainty in every clinical situation,” explains Dr. Sanz. “This work allows us to see much more clearly which tumors have firmly established differences and where substantial uncertainty remains.”
More Than 12,000 Patients and Seven Cancer Types
One of the study’s main innovations is its methodological approach. The researchers conducted an umbrella meta-analysis, a type of analysis that brings together and jointly evaluates evidence from previously published meta-analyses. The study applies this approach for the first time to comprehensively synthesize the available evidence on the efficacy and safety of cisplatin compared with carboplatin across different solid tumors.
“What is innovative is that this is not simply another meta-analysis of a specific tumor but an analysis that, for the first time, comprehensively integrates the available comparative evidence on cisplatin and carboplatin across different cancer types,” explains Dr. Sanz. “This gives us a much broader perspective and, above all, allows us to assess the extent to which the differences we observe are actually supported by solid evidence.”
To build this comprehensive overview, the researchers reviewed the original studies included in each meta-analysis, removed duplicates, and harmonized their results to enable comparisons. In total, the study integrated 11 meta-analyses, 52 original studies, and 12,683 patients, covering seven major tumor groups: urothelial carcinoma, ovarian cancer, cervical cancer, non–small cell lung cancer, small cell lung cancer, gonadal germ cell tumors, and head and neck squamous cell carcinoma.
The analysis included several efficacy outcomes, such as treatment response, overall survival, progression-free survival, and the risk of treatment failure, as well as various adverse effects associated with both drugs. Beyond assessing whether differences exist between cisplatin and carboplatin, the study also determines how much confidence can be placed in each of these conclusions.
To complete this, the researchers used the GRADE system, which rates the certainty of evidence as high, moderate, low, or very low, considering factors such as study design and quality, consistency of results, risk of bias, and precision of estimates. This approach distinguishes between findings that suggest an advantage for one treatment and those supported by evidence robust enough to substantiate it.
The Strongest Evidence Emerges in Urothelial and Ovarian Cancer
The analysis shows that only two outcomes reached a high level of certainty of evidence. In patients with advanced urothelial carcinoma, cisplatin-based treatments were associated with a 38% higher likelihood of achieving an objective response than carboplatin-based treatments. In addition, the likelihood of achieving a complete response was more than twice as high with cisplatin, although the certainty of evidence for this second outcome was moderate.
In this setting, the study lacked equivalent progression-free or overall survival data to determine whether this greater tumor response also translates into a survival benefit. Sensitivity analyses also confirmed the direction of the effect across different study subgroups, although the certainty decreased in some, particularly when the analysis was restricted to randomized clinical trials.
A different picture emerged in advanced ovarian cancer. There is high-certainty evidence that there are no statistically significant differences in progression-free survival between cisplatin- and carboplatin-based treatments, a finding consistent with carboplatin’s current central role in treating this disease. However, this conclusion applies to the setting studied and cannot be directly extrapolated to other settings, such as intraperitoneal chemotherapy.
“These two examples clearly illustrate why we cannot simply say that one platinum drug is better than the other,” explains the researcher. “The answer depends on the tumor type, the stage of the disease, and the treatment goal. In some settings, we have fairly clear differences, while in others we know with considerable confidence that the outcomes are comparable.”
Greater Uncertainty in Other Tumors
In other cancer types, the findings have widely varying levels of certainty. In cervical cancer, cisplatin was associated with a higher likelihood of complete response, with moderate certainty, but no statistically significant differences were found in overall or disease-free survival at three years.
In non–small cell lung cancer, cisplatin achieved a higher objective response rate, although the evidence was of low certainty. By contrast, no significant differences were observed in one-year overall survival or mortality, two findings supported by moderate-certainty evidence. Although this tumor type contributed the largest number of studies and patients to the analysis, the risk of bias in some trials reduced the certainty of certain findings.
Uncertainty was even greater in small cell lung cancer and head and neck tumors, where many findings were based on low- or very low-certainty evidence. In these settings, the available information does not provide a sufficiently robust basis for establishing a difference in efficacy between the two compounds.
In gonadal germ cell tumors, which are particularly relevant because many patients receive treatment with curative intent, the analysis suggested a higher risk of treatment failure with carboplatin. The overall comparison did not reach statistical significance, but certain analyses restricted to studies with more homogeneous methodological characteristics did show differences favoring cisplatin, although the level of certainty remained limited.
Two Drugs With Different Toxicity Profiles
The study also confirms that cisplatin and carboplatin have different toxicity profiles, a key consideration when selecting treatment. Cisplatin was associated with a higher frequency of kidney toxicity, hearing toxicity, and nausea and vomiting, while carboplatin showed greater hematologic toxicity, particularly thrombocytopenia, but also anemia and neutropenia.
No significant differences were found between the two drugs in peripheral neuropathy, and this finding reached a moderate level of certainty. For the other toxicities analyzed, however, the certainty of evidence was very low, partly because of heterogeneity across studies, meaning that the precise magnitude of these differences should be interpreted with caution.
“Efficacy is only one part of the decision,” emphasizes Dr. Sanz. “When choosing a treatment, we also need to consider kidney function, comorbidities, age, hematologic reserve, other treatments the patient is receiving, and the potential impact on their quality of life. Having alternatives with different toxicity profiles allows us to better individualize the treatment strategy.”
Less Robust Evidence Than Might Be Expected
One of the study’s most relevant conclusions is that, although cisplatin and carboplatin have been used for decades and remain a cornerstone of many cancer treatments, the comparative evidence for many tumors and clinical outcomes remains of low or very low certainty. The analysis makes it possible to identify more precisely which decisions are supported by solid evidence while also highlighting the many areas where knowledge gaps persist.
The study also draws attention to an important point in interpreting these findings correctly: finding no statistically significant difference between two treatments does not demonstrate that they are equivalent. Establishing that one treatment is noninferior to another requires trials specifically designed for that purpose, so the absence of differences in some analyses must be interpreted in light of the quality and characteristics of the available evidence.
“This is another significant message from the study,” notes Dr. Sanz. “In some settings, we can say with considerable confidence that we understand the differences between the two treatments, but in others, what we find is that we still lack sufficiently robust evidence to answer certain questions. Identifying these gaps is also important because it shows us where better studies are needed.”
A Tool to Better Individualize Treatment
Overall, the findings show that the choice between cisplatin and carboplatin should consider the cancer type, clinical setting, treatment goal, and each patient’s characteristics, rather than a general assumption that one drug is superior. The review identifies the settings in which current recommendations are supported by higher-certainty evidence and those in which decisions continue to rely on more limited comparative data.
“The ultimate goal is to use all this information to make increasingly individualized decisions,” concludes Dr. Sanz. “It is not just about choosing the potentially most effective treatment but about finding the best option for each patient by balancing disease control, toxicity, and quality of life.”
Reference Article:
Jiménez-Labaig P, Mirallas O, Pereira F, Sanz J, Felip E, Rodon J, Colombo N, Galsky MD, Harrington KJ. Reappraisal of cisplatin vs carboplatin treatment for solid tumors: An umbrella meta-analysis: An umbrella meta-analysis. JAMA Netw Open 2026;9:e2634287. https://doi.org/10.1001/jamanetworkopen.2026.34287.
