Background: Nivolumab improved patients’ survival in metastatic renal cell carcinoma (mRCC). We aimed to evaluate resting energy expenditure (REE) (i.e., patients’ basal metabolism) to predict efficacy. Methods: We conducted a monocentric, observational study of mRCC patients receiving nivolumab between October 2015 and May 2020. REE was measured prior to initiating immunotherapy using indirect calorimetry to determine hypo, normo and hypermetabolism. Primary endpoint was 6-month, progression-free survival (PFS), and secondary endpoints were response rate, PFS and overall survival (OS). Results: Of the 51 consecutive patients, 15 (29%) were hypermetabolic, 24 (47%) normometabolic, and 12 (24%) hypometabolic. The 6-month PFS was 15% for hypermetabolic patients and 65% for non-hypermetabolic patients (p < 0.01). In the multivariate analysis, hypermetabolism was the only baseline factor predicting 6-month PFS (OR 9.91, 95%CI [1.62−60.55], p = 0.01). Disease progression was noted as the best response in 73% of hypermetabolic patients and 26% of non-hypermetabolic patients (p = 0.02). Median PFS was 2.8 and 8.7 months (p < 0.01), and median OS was 20.2 and 35.1 months (p = 0.13) in the hypermetabolic and non-hypermetabolic groups, respectively. Conclusions: Our study identifies an association between mRCC patients’ energy expenditure and nivolumab efficacy. The measurement of REE by indirect calorimetry in routine practice could help identify patients at risk of nivolumab failure.
97 Background: Cabazitaxel rechallenge could be a more efficient therapy with an acceptable toxicity than docetaxel in the treatment of patients with a metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to assess the feasibility and efficacy of cabazitaxel multiple rechallenge. Methods: This is a multicenter, retrospective cohort study including patients from 9 centers in France who received 3 lines or more of cabazitaxel from February 2012 to July 2020. Cabazitaxel schedule differed between patients: 25 mg/m 2 q3w, 20 mg/m 2 q3w, 16 mg/m 2 q2w or 10 mg/m 2 weekly. Efficacy was assessed by overall survival (OS) and progression-free survival (PFS) from each cabazitaxel line start. Only toxicities grade ≥ 3 were reported. Results: Twenty-two patients were included. The median follow-up from mCRPC was 94.7 months, median age at initial diagnosis was 59.5 years old, median ISUP score at diagnosis was 4 and median PSA at diagnosis was 55 ng/ml. Median number of cabazitaxel cycles was 7 at first-line, 6 at first rechallenge, and 5 for subsequent rechallenges. Median OS from mCRPC diagnosis was 105 months. Median PFS from cabazitaxel line start was 11.8 months at first use, 9.6 for first rechallenge and 5.6 in second rechallenge (table). Only one case of febrile neutropenia and 6 events of grade ≥ 3 toxicity were reported. Conclusions: Cabazitaxel multiple rechallenge could efficiently extend OS with manageable toxicities for patients. Even if anti-PARP therapy and immunotherapy are promising treatments, cabazitaxel rechallenge could be also a relevant therapeutic option for long responder patients. Specific biomarkers should be explored to predict the efficacy of cabazitaxel rechallenge. [Table: see text]
Neurotoxicity remains the major dose-limiting toxicity of cisplatin. Peripheral sensory neuropathy, the primary type of cisplatin neurotoxicity, has been reported in 30–100% of patients with clinical symptoms typically developing after cumulative cisplatin doses of $300 mg/m2. Several clinical studies have established an important dose-response, dose intensity-response and cumulative total dose-response relationship for cisplatin in the treatment of head and neck, testicular, melanoma, and ovarian cancers. In patients with these tumor types, the occurrence of moderate or severe neuropathy presents an important therapeutic dilemma. Several types of agents–including micleophilic sulfur thiols, neurotrophic factors, phosphonic acid antibiotics and free oxygen radical scavengers–have been investigated for amelioration of cisplatin-related neurotoxicity. Of these, amifostine is likely to be the first neuroprotective agent widely used to enhance the clinical effectiveness of cisplatin. Recently reported results from a multicenter phase III trial of women with advance ovarian cancer receiving combination chemotheraphy with cisplatin plus cyclophosphamide showed that amifostine pretreatment was associated with moderate but significant reductions in cisplatin-associated peripheral neuropathy, tinnitus and nephrotoxicity, while achieving equivalent pathological response rates and median survival. Preclinical data suggest that several additional agents, especially the neurotropic factors nerve growth factor, insulin-like growth factor-I and neurotrophin-3, merit further investigation. Nerve growth factor is the only agent reported to prevent, rather than partially protect, cisplatin-induced neuropathy in an experimental model.
Cabazitaxel multiple rechallenges may be a treatment option in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) who had a good initial response to cabazitaxel and who are still fit to receive it. Our objective was to assess the efficacy and toxicity of multiple rechallenges.We retrospectively identified 22 mCRPC patients previously treated with docetaxel and/or androgen receptor-targeted agents who received multiple cabazitaxel rechallenges in 9 French centers. Cabazitaxel was initiated at a dose of 25 mg/m2 q3week. A reduced dose (20 mg/m2 q3w) or an alternative schedule (mainly 16 mg/m2 q2w) was increasingly used for subsequent rechallenges. Progression-free survival, prostate-specific antigen (PSA) response, best clinical response, and grade ≥3 toxicities were collected. Overall survival was calculated from various time points.Twenty-two patients with an initial response to cabazitaxel were rechallenged at least twice. The median number of cabazitaxel cycles was 7 at first cabazitaxel treatment, 6 at first rechallenge, and 5 at subsequent rechallenges. Median progression-free survival at first rechallenge was 9.6 months and 5.6 months at second rechallenge. Median overall survival was 50.9 months from the first cabazitaxel dose, 114.9 months from first life-extending therapy initiation in mCRPC, and 105 months from mCRPC diagnosis. There was no cumulative grade ≥3 neuropathy or nail disorder and one case of febrile neutropenia.Cabazitaxel multiple rechallenges may be a treatment option without cumulative toxicity in heavily pretreated patients having a good response to first cabazitaxel use and still fit to receive it.Patients with metastatic castration-resistant prostate cancer can be treated with Cabazitaxel after docetaxel and androgen receptor-targeted agent. This chemotherapy can be used multiple times with efficacy and manageable toxicity.
