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Chemotherapy efficacy after first-line immunotherapy in 18 advanced melanoma patients.

ABSTRACT: In BRAF wild type advanced melanoma, immune checkpoint blockers such as anti-PD1 (anti-programmed cell death 1) are usually continued beyond progression for a hypothetical rare further response. Chemotherapy as a second-line option is considered ineffective by many practitioners based on historical data. Continuing anti-PD1 beyond progression has a high health-economic impact and is not recommended by the FDA. This study aimed to describe the efficacy and survival of advanced melanoma patients who received second-line (or more) chemotherapy after immunotherapy failure.This was a retrospective single center study conducted in a French University Hospital during an 11-month period. All advanced melanoma patients treated with chemotherapy after immunotherapy failure were included.Eighteen patients were analyzed. Therapeutic response to chemotherapy was evaluable in 16 patients: partial response was achieved in 3/16 (19%), stable disease in 1/16 (6%) and progressive disease in 12/16 (75%). Median overall survival from chemotherapy start was 12 months. Median progression-free survival was 5.4 months. The 6-month overall survival rate was 81% and the 6-month progression-free survival rate was 40%.Although the disease control rate with chemotherapy was low (25%), survival data in our study are far superior to those previously published. This could be linked to a high proportion of patients treated with anti-PD1 just prior to chemotherapy, which may suggest a potential synergy between immunotherapy and chemotherapy.

SUBMITTER: Saint-Jean M

PROVIDER: S-EPMC7373626 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Chemotherapy efficacy after first-line immunotherapy in 18 advanced melanoma patients.

Saint-Jean Mélanie M Fronteau Clémentine C Peuvrel Lucie L Khammari Amir A Varey Emilie E Quéreux Gaëlle G Dréno Brigitte B

Medicine 20200701 29

In BRAF wild type advanced melanoma, immune checkpoint blockers such as anti-PD1 (anti-programmed cell death 1) are usually continued beyond progression for a hypothetical rare further response. Chemotherapy as a second-line option is considered ineffective by many practitioners based on historical data. Continuing anti-PD1 beyond progression has a high health-economic impact and is not recommended by the FDA. This study aimed to describe the efficacy and survival of advanced melanoma patients w ...[more]

PMID: 32702928

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Project description:AimTo compare the efficacy and safety of radiotherapy in combination with immunotherapy after achieving disease control from the first-line combination therapy of platinum-based chemotherapy and immunotherapy for advanced lung squamous cell carcinoma (LUSC).MethodsThis study retrospectively evaluated the patients with advanced LUSC treated with the combination of radiotherapy with immunotherapy and chemotherapy (ICRT group, n = 52) or immunotherapy and chemotherapy (ICT group, n = 63) as the first-line treatment from April 2018 to April 2022. Using propensity score matching (PSM), 50 pairs were created, while the confounders and bias were controlled. The objective response rate (ORR), duration of overall response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed in the two groups. The PFS and OS were re-analyzed separately for patients treated with thoracic radiotherapy.ResultsAfter PSM, the median PFS (12.23 vs. 7.43 months; P <0.001) and median OS (19.7 vs. 12.9 months; P <0.001) were significantly longer in the ICRT group than those in the ICT group. Both the PFS and OS rates were also significantly higher in the ICRT group than those in the ICT group, except for the OS rates in the 6th and 12th months. The mDOR of the ICRT group patients (17.10 vs. 8.27 months; P <0.001) was significantly higher than that of the ICT group patients. The median PFS, median OS, and local control rate were significantly longer in the thoracic radiotherapy group than in the control group. Radiation pneumonia was the most common adverse effect after radiotherapy; however, no treatment-related deaths occurred. The Cox regression analysis showed that ECOG scores 0-1, presence of necrosis in the tumor, radiotherapy, and optimal efficacy better than the stable disease (SD) were independent factors, affecting the PFS, while the patients with recurrent post-operative, pre-treatment NLR, radiotherapy, and optimal efficacy better than SD were the independent factors, affecting the OS.ConclusionsThe combination of radiotherapy with systematic immunotherapy and chemotherapy for the advanced LUSC was effective with tolerable adverse effects.

Project description:BackgroundRecent advances in targeted therapy and immunotherapy have improved the prognosis of melanoma patients but brain metastasis remains a major challenge. Currently, it is unclear how existing therapies can be best used to prevent or treat brain metastasis in melanoma patients.AimsWe aimed to assess brain metastasis free survival (BMFS), overall survival (OS), incidence of brain metastases, and sequencing strategies of immunotherapy and targeted therapy in patients with BRAF-mutated advanced melanoma.Methods and resultsWe retrospectively analyzed 683 patients with BRAF-mutated advanced melanoma treated with first line (1L) immunotherapy (N = 266) or targeted therapy (N = 417). The primary outcome was BMFS. Secondary outcomes included OS of all patients and incidence of brain metastases in patients without documented brain metastases prior to 1L therapy. The median BMFS was 13.7 months [95% confidence interval (CI): 12.4-16.0] among all patients. The median BMFS for patients receiving 1L immunotherapy was 41.9 months [95% CI: 22.8-not reached (NR)] and targeted therapy was 11.0 months (95% CI: 8.8-12.5). Median OS results were qualitatively similar to BMFS results. The cumulative incidence of brain metastases for patients receiving 1L targeted therapy was higher than for patients receiving 1L immunotherapy (P < .001). Patients receiving 1L anti-CTLA4 plus anti-PD1 combination immunotherapy only or followed by second line (2L) targeted therapy had better BMFS (HR 0.40, 95% CI: 0.24-0.67, P = .001), improved OS (HR 0.49, 95% CI: 0.30-0.81, P = .005), and reduced incidence of brain metastases (HR 0.47, 95% CI: 0.24-0.67, P = .047) than patients receiving 1L combination BRAF and MEK targeted therapy followed by 2L immunotherapy.ConclusionPatients with advanced BRAF mutant melanoma treated with 1L immunotherapy have significantly longer BMFS and OS, and reduced incidence of brain metastases, compared with those treated with 1L targeted therapy. Further studies evaluating the ability of immunotherapy and targeted therapy to improve OS and prevent brain metastases are warranted.

Dataset Information

Chemotherapy efficacy after first-line immunotherapy in 18 advanced melanoma patients.

Publications

Chemotherapy efficacy after first-line immunotherapy in 18 advanced melanoma patients.

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