Tumour size strongly predicts survival in advanced melanoma
A smaller tumour at baseline translates to better survival for advanced melanoma patients receiving treatment with the PD-L1 inhibitor pembrolizumab as compared with a bigger tumour, according to a posthoc analysis of the KEYNOTE-001 trial.
The results indicate that baseline tumour size (BTS) is an independent marker of prognosis in advanced melanoma, the investigators said. If validated, tumour size at baseline should prove useful for risk stratification of patients in future clinical studies.
A total of 583 patients with baseline measurable disease, representing 89 percent of the total KEYNOTE-001 population, were included in the present analysis. Median age was 61 years, and median BTS was 10.2 cm. BTS was below median in half of the patients.
Patients with larger median BTS were more likely to have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1, elevated lactate dehydrogenase (LDH), stage M1c disease and liver metastases (p≤0.001 for all).
Univariate Cox regression analysis revealed that BTS below the median was associated with higher objective response rate (ORR; 44 percent vs 23 percent; p<0.001) and longer overall survival (OS; hazard ratio [HR], 0.38; p<0.001). BTS below the median remained strongly predictive of OS (p<0.001) but not ORR in multivariate models. [Clin Cancer Res 2018;24;4960-4967]
In the subgroup of 459 patients with data on tumour programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1–positive disease were independently associated with higher ORR and longer OS.
“Our data suggest that there is a greater unmet medical need in patients with a larger BTS, a group that typically includes previously treated patients, which thereby supports use of PD-1 inhibitors earlier in the disease course,” the investigators said.
“One of the more interesting findings of our analysis was the exceptionally good outcomes for patients with lung-only metastases; these patients experienced a near tripling of ORR compared with patients with liver metastases (62 percent vs 22 percent). Although independent validation of this finding is necessary, if confirmed, this information could aid in clinical decision making,” they added.
In a linked commentary, Drs Allison Betof Warner and Michael Postow from the Memorial Sloan Kettering Cancer Center in New York, US, noted that the present posthoc KEYNOTE-001 data indicate that bigger is not better, with patients having larger BTS generally doing less well. [Clin Cancer Res 2018;24;4915-4917]
However, Betof Warner and Postow pointed out that the data fall short of facilitating the use of BTS to select treatment for patients.
“BTS could prove to be incredibly helpful if larger, additional studies confirm its prognostic role. One could conceive patients being stratified by BTS in future clinical trials, as is currently practice for elevations in LDH,” they said, adding that BTS could eventually become part of clinical staging systems given the relative ease of measurement.
“Despite needed additional development of BTS prior to routine clinical use in treatment selection and trial stratification, the [current] data help set realistic expectations in patient conversations, as the complete response rate to pembrolizumab in patients with BTS above the median was unfortunately only 2 percent compared to a much more favourable 18 percent for patients with BTS below the median,” they continued.
Larger randomized studies are warranted to explore the utility of BTS in treatment decisions for individual patients, as well as better understand the immunologic implications of larger or even smaller tumour burdens in the presence of elevated LDH or liver metastases, according to Betof Warner and Postow.