Immunotherapy Potentiates the Effect of Chemotherapy in Metastatic Melanoma—A Retrospective Study

Hadash-Bengad, Reut; Hajaj, Emma; Klein, Shoshana; Merims, Sharon; Frank, Stephen Jay; Eisenberg, Galit; Yakobson, Alexander; Orevi, Marina; Caplan, Nadia; Peretz, Tamar; Lotem, Michal; Cohen, Jonatan E.

doi:10.3389/fonc.2020.00070

Cited by 33 publications

(39 citation statements)

References 25 publications

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“…Median PFS was significantly longer in the group receiving chemotherapy after immunotherapy (respectively 5.2 vs 2.5 months, P = .046). [ 11 ] Another Japanese retrospective study of 9 patients treated with chemotherapy after immunotherapy showed comparable outcome results (mean PFS 5.0 months and mean OS 7.6 months). [ 12 ] Several hypotheses can be advanced to explain this better prognosis, including selection bias of long-responder patients, or continuation of the immunotherapy effect after its discontinuation.…”

Section: Discussionmentioning

confidence: 99%

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

Saint‐Jean

Fronteau²,

Peuvrel

et al. 2020

Medicine

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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.

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Section: Discussionmentioning

confidence: 99%

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

Saint‐Jean

Fronteau²,

Peuvrel

et al. 2020

Medicine

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“…On the other hand, in a multicenter retrospective study of R/M HNSCC, a taxane-based regimen after ICI was associated with higher ORR than other chemotherapy regimens (53 vs. 25%, p = 0.024) ( 35 ). Also, according to a retrospective study of metastatic melanoma, an increased proportion of CD8-positive cells with elevated PD-1 and CD69 expression was observed while on chemotherapy as compared with all-time points on ICIs, suggesting immune-activation by interaction of chemotherapy and ICIs ( 36 ). For R/M HNSCC, pembrolizumab or pembrolizumab+platinum+5FU showed significantly better OS than the EXTREME regimen and became a standard first-line treatment ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Combination Treatment With Paclitaxel, Carboplatin, and Cetuximab (PCE) as First-Line Treatment in Patients With Recurrent and/or Metastatic Nasopharyngeal Carcinoma

et al. 2020

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Background: Platinum-containing doublet chemotherapy regimens are generally considered the standard first-line systemic therapy for recurrent or metastatic (R/M) nasopharyngeal cancer (NPC). Gemcitabine (GEM) plus cisplatin (CDDP) has become a standard therapy based on a phase 3 study in several countries, yet this regimen sometimes affects quality of life due to nausea or appetite loss. Here, we present the manageable toxicity and promising activity of paclitaxel + carboplatin + cetuximab (PCE) therapy for R/M NPC. Materials and Methods: We conducted a retrospective review of patients with R/M NPC who were treated with PCE from 2013 to 2019 at the National Cancer Center East, Kashiwa, Japan. PCE consisted of PTX 100 mg/m 2 on days 1 and 8; CBDCA area under the blood concentration-time curve (AUC) 2.5 on days 1 and 8, repeated every 3 weeks; and cetuximab at an initial dose of 400 mg/m 2 , followed by 250 mg/m 2 weekly, as reported in the paper. Results: Fourteen patients were identified, consisting of 10 males and 4 females with a median age 59.6 years (range, 43-74). Among the 12 of 14 patients assessed for efficacy, overall response rate was 58.3%, with 2 complete responses and 5 partial responses. On median follow-up of 23.8 months, median overall survival was not reached with observed death events of 2. Median PFS was 4.1 months (95% CI, 2.6-5.6 months). Two patients experienced disease progression during cetuximab maintenance and restarted PCE treatment, then achieved partial response again. The most common grade 3 or 4 adverse events were neutropenia (21.4%) and skin reaction (14.3%). No treatment-related death was observed. Conclusion: Although the number of study population was small, our results suggest that PCE is feasible and potentially effective for R/M NPC, with a 58.3% response rate and 4.1-month PFS. Further prospective evaluation is warranted.

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“…However, since cetuximab remains a key chemotherapy drug for R/M SCCHN, it is expected that cetuximab is increasingly used as a second- or later-line setting after exposure to immunotherapy. Several studies have demonstrated potential improvements in the treatment outcomes of cytotoxic chemotherapy after exposure to immunotherapy in various types of malignancies, including malignant melanoma, non-small cell lung cancer and stomach cancer [ 7 – 9 ]. In R/M SCCHN, two retrospective studies assessed patients who progressed on ICIs and subsequently underwent cytotoxic chemotherapy; these studies reported a relatively higher overall response rate (ORR) [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study

Kurosaki¹,

Mitani²,

Tanaka³

et al. 2020

Anti-Cancer Drugs

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Immunotherapy has been shown to prolong survival in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in front-line use; however, subsequent systemic therapy has not been optimized. This study aimed to evaluate the safety and efficacy of cetuximab-containing chemotherapy after immunotherapy. We retrospectively analyzed patients with recurrent or metastatic SCCHN who underwent cetuximab-containing regimens after progression on immunotherapy. Of the 22 patients who met the inclusion criteria, 21 received paclitaxel and cetuximab, and 1 carboplatin and fluorouracil and cetuximab after immunotherapy. Nine patients achieved a partial response, 10 patients had stable disease as their best response on cetuximab-containing chemotherapy, yielding an overall response rate and disease control rate of 40.9 and 86.4%, respectively. The median progression-free survival was 5.2 months, and the median overall survival was 14.5 months. Ten patients developed grade 3–4 adverse events, including neutropenia (31.8%), acneiform rash (9.1%), anemia (4.5%), hypertransaminasemia (4.5%) and stomatitis (4.5%). The most frequent cetuximab-related toxicities across all grades were skin reactions (77.3%), hypomagnesemia (40.9%), stomatitis (27.3%), paronychia (13.6%) and keratitis (4.5%). There was no treatment-related death. Taken together, cetuximab-containing chemotherapy was effective and feasible even after immunotherapy.

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Immunotherapy Potentiates the Effect of Chemotherapy in Metastatic Melanoma—A Retrospective Study

Cited by 33 publications

References 25 publications

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

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

Combination Treatment With Paclitaxel, Carboplatin, and Cetuximab (PCE) as First-Line Treatment in Patients With Recurrent and/or Metastatic Nasopharyngeal Carcinoma

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study

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