TPExtreme randomized trial: Quality of Life (QoL) and survival according to second-line treatments in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).

Abstract

6507 Background: TPExtreme trial comparing EXTREME regimen to the taxane-based TPEx confirmed the encouraging survival results of the TPEx regimen, despite lack of significant overall survival (OS) increase, with a significantly lower toxicity than the EXTREME regimen. Herein, the QoL and exploratory analyses of survival according to 2nd line treatments focusing on immunotherapy (IO) are presented. Methods: Randomized (1:1), open-label trial. Main inclusion criteria were R/M HNSCC not suitable for loco-regional treatment, age 18-70 years, PS < 2, creatinin clearance > 60ml/min, prior cisplatin < 300 mg/m². 539 pts were enrolled over a period of 37 months (mo). QoL was evaluated with QLQ-C30 questionnaire at baseline, week(W)12, W18, W26 and analyzed by linear mixed model. The primary QoL endpoint was the Global Health Status score. 2nd line treatments were collected for 501 (93%) patients (pts), 256 in the EXTREME arm and 245 in the TPEx arm. Results: The percentage of QLQ-C30 questionnaires filled at baseline, W12, W18 and W26 were similar in the 2 arms, 89%, 52%, 43%, and 39% in the EXTREME arm and 91%, 59%, 40%, and 37% in the TPEx arm, respectively.. Higher scores of Global Health Status (p = 0.02), physical functioning (p = 0.009) and role functioning (p = 0.013) and lower scores of appetite loss (p = 0.041) were observed in the TPEx arm than in the EXTREME arm. No significant difference was observed for the other scores. In 2nd line treatment, 120 (47%) pts in the EXTREME arm and 109 (44%) in the TPEx arm received chemotherapy +/- cetuximab (CT); 41 (16%) pts in the EXTREME arm and 41 (17%) in the TPEx arm received IO, mainly anti-PD-1/PD-L1. 79% and 85% of these 2nd line treatments were given after progression in EXTREME and TPEx arms respectively. Median OS (95%CI) since randomization was 17.6 (15.2 – 19.5) mo with CT and 19.4 (13.4 – 22.3) mo with IO in the EXTREME arm vs 14.9 (13.0 – 16.3) and 21.9 (15.9 – 35.0) mo in the TPEx arm (interaction test p = 0.077) respectively. Median OS since start of 2nd line was 9.3 mo with CT and 8.3 mo with IO in the EXTREME arm, and 7.1 and 11.6 mo respectively in the TPEx arm. Conclusions: An improvement in the QoL of patients was observed in the TPEx arm compared to that of the EXTREME arm. Exploratory analysis showed that the taxane-based TPEx regimen followed by IO in 2nd line could provide interesting median OS for pts who need CT in 1st line, with less toxicity than EXTREME. This sequential treatment deserves to be compared to a strategy that starts with Platinum+5FU+pembrolizumab. Clinical trial information: NCT02268695 .

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

“…In a phase 3 clinical trial of breast cancer, combination therapy of nab-paclitaxel and the anti PD-L1 inhibitor atezolizumab showed prolonged PFS over nab-paclitaxel alone in the PD-L1-positive subgroup ( 33 ). Besides, in the exploratory analysis of 2nd-line therapy after either TPExtreme regimen, which was combination therapy of docetaxel+CDDP+Cmab, or ETREME regimen in R/M HNSCC, patients treated with ICI showed longer OS compared with those with chemotherapy in both regimens; however, this trend was more potent in TPExtreme (interaction test p = 0.077) ( 34 ). This result also suggested that the use of taxane prior to ICI presumably augments the effect of subsequent ICI and supports our hypothesis that PTX may enhance the response to nivolumab.…”

Immunotherapy Breakthroughs in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

“…Thus, other strategies are worth discussing. In the TPExtreme study, a first line chemotherapy with a taxane (TPEx) followed by second line with immunotherapy yields a 21.9 month median survival [37]. In the end, in order to determine which would be the best strategy, a randomized trial should be conducted comparing TPEx followed by immunotherapy vs. pembrolizumab + chemotherapy in first line.…”

Cisplatin, Docetaxel and Cetuximab (TPEx) as First-line Treatment for Patients With Recurrent or Metastatic Head and Neck Cancer: A Multicenter Real-World Study

“…TPEx regimen was associated with 30% grade 4 adverse events, which was signi cantly lower than the 43% incidence reported with the EXTREME schema. Furthermore, an exploratory analysis of this trial showed a better quality of life in patients who received TPEx, mainly in global health status, physical functioning, role functioning, and scores of appetite20 .Remarkably, real-world data in this setting is scarce. Before the GORTEC trial, Guigay and collaborators presented the results of 30 patients treated with TPEx at Gustave Roussy Institute between 2011 and 201321 .…”