Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors: An overlooked aspect in immunotherapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy but frequently cause immune-related adverse events (irAEs). Description of late-onset and duration of irAEs in the literature is often incomplete. METHODS: To investigate reporting and incidence of late-onset and long-lasting irAEs, we reviewed all registration trials leading to ICI's approval by the US FDA and/or EMA up to December 2019. We analysed real-world data from all lung cancer (LC) and melanoma (Mel) patients treated with approved ICIs at the University Hospital of Lausanne (CHUV) from 2011 to 2019. To account for the immortal time bias, we used a time-dependent analysis to assess the potential association between irAEs and overall survival (OS). RESULTS: Duration of irAEs and proportion of patients with ongoing toxicities at data cut-off were not specified in 56/62 (90%) publications of ICIs registration trials. In our real-world analysis, including 437 patients (217 LC, 220 Mel), 229 (52.4%) experienced at least one grade ≥2 toxicity, for a total of 318 reported irAEs, of which 112 (35.2%) were long-lasting (≥6 months) and about 40% were ongoing at a median follow-up of 369 days [194-695] or patient death. The cumulative probability of irAE onset from treatment initiation was 42.8%, 51.0% and 57.3% at 6, 12 and 24 months, respectively. The rate of ongoing toxicity from the time of first toxicity onset was 42.8%, 38.4% and 35.7% at 6, 12 and 24 months. Time-dependent analysis showed no significant association between the incidence of irAEs and OS in both cohorts (log Rank p = 0.67 and 0.19 for LC and Mel, respectively). CONCLUSIONS: Late-onset and long-lasting irAEs are underreported but common events during ICIs therapy. Time-dependent survival analysis is advocated to assess their impact on OS. Real-world evidence is warranted to fully capture and characterise late-onset and long-lasting irAEs in order to implement appropriate strategies for patient surveillance and follow-up.

Use of low-level laser therapy (LLLT) or photobiomodulation (PBM) for the management of the hand-foot syndrome (HSF) or palmo-plantar erythrodysesthesia (PPED) associated with cancer therapy.

The purpose of this pilot study was to determine whether photobiomodulation (PBM) might be effective for chemotherapy-induced palmo-plantar erythrodyesthesia (PPED), as it is for mucositis or radio dermatitis; no standard therapy exists for PPED. Patients were allocated to PBM or sham irradiation and were blindly assessed after 2 weeks. Pain and satisfaction with treatment were also evaluated. We found a significant benefit from PBM in comparison with sham treatment (p < 0.03) and a decrease of pain in 49% of the patients. No adverse reactions were observed. We concluded that PBM might represent a useful approach for the management of PPED.

[Tamoxifen induced thromboembolic events in breast cancer. Some possible mechanisms]. / Evénements thromboemboliques induits par le tamoxifène dans le cancer du sein. Certains mécanismes potentiels.

Tamoxifen is an antagonist of the oestrogen receptor, used in the treatment of breast cancer. It is known to reduce osteoporotic bone fractures, but it increases the risk of endometrial tumors and venous thromboembolic events (VTEs). VTEs increased significantly during tamoxifen therapy within 3 months of major surgery, immobilization or fracture. Their incidence is associated with patients' risk factors, tumor and tissue induced procoagulation. The mechanisms are still not well known. There is a need for a better understanding in order to develope a prophylactic and therapeutic strategy.

Le tamoxifène est un antagoniste du récepteur de l'oestrogène, utilisé dans le traitement du cancer du sein. Le rôle du tamoxifène dans la réduction du risque de fractures osseuses ostéoporotiques est connu. Par contre il augmente le risque d'apparition de tumeurs de l'endomètre et des événements thromboemboliques veineux (ETEV). L'incidence d'ETEV augmente de manière significative au cours du traitement par le tamoxifène dans les 3 mois d'une chirurgie majeure, suite à une immobilisation ou une fracture. L'incidence est associée aux facteurs de risque des patients et à une hyper coagulabilité tumeur ou tissu induite. Les mécanismes thromboemboliques liés au tamoxifène ne sont pas encore bien connus. Il est nécessaire de mieux les connaître pour développer une stratégie prophylactique et thérapeutique.

Bisphosphonate-related osteonecrosis of the jaw: a review of the potential efficacy of low-level laser therapy.

Osteonecrosis of the jaw (ONJ) resulting from administration of bisphosphonates (BP) or denosumab is a rare but severe complication in cancer patients. Complete remission depends on the stage of ONJ; it can be estimated in the range of 20-30 %. Low-level laser therapy (LLLT) is a logical additional option, as it has been recognized effective for the management of chemotherapy and/or radiotherapy-induced mucositis. LLLT irradiation has anti-inflammatory actions and thus can help to control pain, as well as biostimulating properties with favorable actions on bacterial control and wound healing. We review the results of seven published studies of LLLT in BP-associated ONJ. LLLT results in an overall response rate of 55 % superior to that observed in controls (30 %). Our review suggests that there might be an advantage to add LLLT to the "classical" management of ONJ. This therapy is easy to administer and is not associated with any known side effects. Further research is needed to remove any doubt of protection or enhancement of carcinogenic processes. We believe that prospective well-controlled studies of LLLT in ONJ are warranted. If the positive results are confirmed, it would represent a great improvement for the quality of life of many patients.

Role of corticosteroids in prostate cancer progression: implications for treatment strategy in metastatic castration-resistant patients.

Corticosteroid agents (CA) are widely used in the treatment of metastatic castration-resistant prostate cancer (mCRPC) either as concomitant treatment with active agents such as docetaxel, cabazitaxel and abiraterone or in a palliative setting, predominantly due to their anti-inflammatory activity. However, the chronic use of CA has numerous side effects, especially in case of steroid-induced adrenal insufficiency. Furthermore, the latest clinical and preclinical data demonstrate that CA themselves are likely to promote tumour progression in certain populations of patients with mCRPC. Therefore, the role of CA in advanced disease should be carefully weighed for each patient and their withdrawal should be considered in some patients. This is necessary, especially in clinical trials that need good performance status patients to evaluate the activity and the safety of emerging drugs in mCRPC that do not require the concurrent use of CA. In oncology, there is no consensus on an algorithm of gradual steroid tapering and frequently the approach to this procedure is empirical. An algorithm is presented in this article based on clinical observations. Prospective studies are necessary to evaluate the efficacy and safety of the above-proposed algorithm in metastatic castration-resistant prostate cancer.