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. 2024 Oct 1;24(1):1220.
doi: 10.1186/s12885-024-12961-9.

Weekly carboplatin plus paclitaxel chemotherapy in advanced melanoma patients resistant to anti-PD-1 inhibitors: a retrospective, monocentric experience

Francesca Romana Di Pietro #  1 , Daniele Marinelli #  2 , Sofia Verkhovskaia  1 , Giulia Poti  1 , Rosa Falcone  1 , Maria Luigia Carbone  3 , Maria Francesca Morelli  1 , Albina Rita Zappalà  1 , Zorika Christiana Di Rocco  1 , Roberto Morese  1 , Gabriele Piesco  1 , Paolo Chesi  1 , Paolo Marchetti  1 , Cristina Maria Failla #  4 , Federica De Galitiis #  1
Affiliations

Weekly carboplatin plus paclitaxel chemotherapy in advanced melanoma patients resistant to anti-PD-1 inhibitors: a retrospective, monocentric experience

Francesca Romana Di Pietro et al. BMC Cancer. .

Abstract

Immunotherapy with anti-PD-1 antibodies significantly improved the prognosis in advanced melanoma patients, but most of them develop primary or secondary resistance to the treatment. In this study, we evaluated efficacy and safety of a chemotherapy regimen with weekly carboplatin plus paclitaxel (wCP) in patients previously treated with anti-PD-1 antibodies. We retrospectively identified 30 patients with advanced melanoma treated at our Institute over the last eight years with wCP. The co-primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). In addition, we evaluated treatment tolerability. For this patient cohort, median PFS and OS were 3.25 and 7.69 months, respectively. All included patients had previously received anti-PD-1 immunotherapy, most of them had ECOG PS 0-1, and only 5 patients had a BRAF V600 mutation. In univariable analysis, we observed shorter OS in patients with > 2 involved metastatic sites, superficial spreading histology, and serum lactate dehydrogenase (LDH) values above the median. Liver metastases were associated with worse outcomes, while radiotherapy treatment of brain metastases was associated with improved OS. However, in a multivariable Cox regression model, only LDH above the median, superficial spreading histology, and female sex were significantly associated with worse OS. We reported grade 3 and 4 treatment-related toxicities in 4 and 0 patients, respectively. In conclusion, chemotherapy with wCP is a valid palliative treatment in advanced melanoma who progressed with anti-PD-1 antibodies.

Keywords: Immunoresistance; Melanoma; Palliative treatment; Platinum-based chemotherapy.

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Conflict of interest statement

The authors declare no competing interests.

FdG has been a speaker at BMS, and Novartis conference. PM had a consultant/advisory role for BMS, ROCHE Genentech, MSD, Novartis, AMGEN, Merck Serono, Pierre Fabre, INCYTE. The two authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Kaplan-Meier estimation of PFS and OS in the overall population (A) PFS in patients treated with wCP; median PFS was 3.25 months. (B) OS in patients treated with wCP; OS was 7.69 months. PFS: progression free survival; OS: overall survival; wCP: weekly carboplatin plus paclitaxel; CI: confidence interval; No: number
Fig. 2
Fig. 2
PFS and OS according to burden disease in patients treated with wCP. (A) PFS in the whole study population according to burden disease. mPFS was of 18.81 months in patients with 1–2 metastatic site and of 2.61 months in patients with > 2 metastatic sites. (B) OS in the whole study population according to burden disease. mOS was 28.64 months in patients with 1–2 metastatic site and 4.96 months in patients with > 2 metastatic sites. PFS: progression free survival; OS: overall survival; wCP: weekly carboplatin plus paclitaxel; CI: confidence interval; mPFS: median PFS; mOS: median OS; No: number
Fig. 3
Fig. 3
PFS and OS according to presence/absence of liver metastasis in patients treated with wCP. (A) PFS in the whole study population according to presence/absence of liver metastasis. mPFS was of 4.39 months in patients without liver metastasis and of 2.66 months in patients with hepatic sites of disease. (B) OS in the whole study population according to presence/absence of liver metastasis. mOS was 8.83 months in patients without liver metastasis and 2.62 months in patients with hepatic sites of disease. PFS: progression free survival; OS: overall survival; wCP: weekly carboplatin plus paclitaxel; CI: confidence interval; mPFS: median PFS; mOS: median OS; mets: metastases; No: number
Fig. 4
Fig. 4
PFS and OS according to LDH level in patients treated with wCP. (A) PFS in the whole study population according to LDH levels. mPFS was of 6.15 months in patients with LDH level less than median value and of 2.17 months in patients with LDH level greater than median value. In patients with unknown LDH value mPFS was 3.42 months. (B) OS in the whole study population according to LDH levels. mOS was 9.96 months in patients with LDH level less than median value and of 2.75 months in patients with LDH level greater than median value. In patients with unknown LDH value mOS was 8.61 months. PFS: progression free survival; OS: overall survival; LDH: lactate dehydrogenase; wCP: weekly carboplatin plus paclitaxel; CI: confidence interval; mPFS: median PFS; mOS: median OS; No: number
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