ABSTRACT
Background and Aims: The treatment of metastatic non-small-cell lung cancer (NSCLC) has been revolutionized by the arrival of immune checkpoint inhibitors (ICI). For patients without immune related adverse events (irAEs), it is recommended to continue the treatment as long as it provides clinical benefit or until unacceptable toxicity appears. The aim of our study was to evaluate survival data among patients with advanced or metastatic NSCLC following ICI discontinuation for reasons of long-term response or toxicity (irAEs). Methods: We included all patients with advanced or metastatic NSCLC treated with nivolumab and pembrolizumab at the Centre Jean Perrin, Clermont-Ferrand, France (January 1, 2016 to May 31, 2019). We focused on two groups in this study population: "Voluntary treatment discontinuation" (medical decision as a result of long-term response and patient decision) and "Treatment discontinuation due to toxicity" (irAEs). The primary endpoint was to evaluate the postdiscontinuation outcomes of these two groups: progression-free survival (PFS) and overall survival (OS), and rechallenge in the "voluntary discontinuation" group. Results: The final analysis concerned 146 patients, including 10 (7%) in the "discontinuation due to toxicity" group, 11 (8%) in the "voluntary discontinuation" group, 100 (68%) who discontinued treatment as a result of progression and 25 (17%) whose treatment was still on-going. The median PFS in the "discontinuation due to toxicity" group was not reached, and in the "voluntary discontinuation" group (n = 11) was 37 months (p = 0.4), versus 2 months in the progression group (p < 0.001). The median OS in "discontinuation due to toxicity," and in the "voluntary discontinuation" groups was not reached (p = 0.5), versus 10 months in the progression group (p < 0.001). Conclusion: Treatment discontinuation following long-term response to ICI treatment showed sustained response and long-term survival after discontinuation. The incidence of irAEs was associated with better long-term survival, even after ICI discontinuation.
ABSTRACT
BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) patients have a poor prognosis, and curcumin is known to have antineoplastic properties. On the basis of previous phase I and phase II studies, we investigated whether the association of curcumin with docetaxel could improve prognosis among mCRPC patients. METHODS: A total of 50 mCRPC patients (included from June 2014 to July 2016) treated with docetaxel in association with oral curcumin (6 g/d for 7 days every 3 weeks) versus placebo were included in this double-blind, randomized, phase II study. The primary endpoint was to evaluate the time to progression. Among the secondary endpoints, compliance, overall survival, prostate-specific antigen (PSA) response, safety, curcumin absorption, and quality of life were investigated. An interim analysis was planned in the modified intention-to-treat population with data at 6 months (22 patients per arm). RESULTS: Despite good compliance and a verified absorption of curcumin, no difference was shown for our primary endpoint: progression-free survival (PFS) between the placebo and curcumin groups was, respectively, 5.3 months versus 3.7 months, p = 0.75. Similarly, no difference was observed for the secondary objectives: PSA response rate (p = 0.88), overall survival (p = 0.50), and quality of life (p = 0.49 and p = 0.47). CONCLUSION: Even though our previous studies and data in the literature seemed to support an association between curcumin and cancer therapies in order to improve patient outcome and prognosis, the results from this interim analysis clearly showed that adding curcumin to mCRPC patients' treatment strategies was not efficacious. The study was discontinued on the grounds of futility.
