Anti-PD-1 for the treatment of advanced cutaneous squamous cell carcinoma in elderly patients: a French multicenter retrospective survey.

BACKGROUND: Anti-PD1 agents are currently recommended as first-line treatment in advanced cutaneous squamous cell carcinoma (acSCC) by updated European guidelines. Although acSCC frequently affects elderly patients with multiple comorbidities, this subset of patients is often excluded of registration clinical trials. PURPOSE: To assess anti-PD-1 efficacy and safety in elderly acSCC patients in real-life conditions and describe this specific population with oncogeriatric evaluation tools. METHODS: A multicenter retrospective study including acSCC patients at least 70 years old treated with PD-1 inhibitors was conducted in French referral centers. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety data, time to response (TTR), duration of response (DOR), overall survival (OS), and progression-free survival (PFS). RESULTS: 63 patients were included. ORR was 57.1% (95% CI 44.0-69.5), median TTR and DOR were 3 and 5.5 months respectively. Median OS was not reached (95% CI 12.5 months-not reached) at data cut-off after a median follow-up of 8 months while median PFS was 8 months. (95% CI 5 months-not reached). Grade 3-5 adverse effects occurred in 47.6% of patients. 41.3% of patients experienced degradation of ECOG performance status during anti-PD-1 treatment. Nutritional state worsened in 27% of patients and 57.1% lost weight during treatment. CONCLUSION: In this particular subset of acSCC patients PD-1 inhibitors obtain results similar to those obtained in younger populations included in pivotal clinical trials, with acceptable safety. A specific oncogeriatric evaluation at treatment initiation and during follow-up appears important in this setting most notably to help manage toxicity.

Immuno-oncology therapy in metastatic bladder cancer: A systematic review and network meta-analysis.

CONTEXT: Three first line and three second-line clinical trials tested the effect of immunotherapy (IO) relative to standard chemotherapy (CT) on overall survival. However, network meta-analysis-based comparisons have not yet been presented. We addressed this void. OBJECTIVE: To provide comparisons of overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), objective response rates (ORR), disease control rates (DCR) and adverse events (AEs) associated with 1st and 2nd line IO-based regimens. MATERIALS AND METHODS: PubMed was searched for phase III randomized controlled trials from 2016 to 2021, including conference abstracts. We identified three first line [IMvigor130 (atezolizumab + CT vs atezolizumab vs CT), DANUBE (durvalumab vs durvalumab + tremelimumab vs CT), and KEYNOTE-361 (pembrolizumab + CT vs pembrolizumab vs CT)] and two second line [KEYNOTE-045 (pembrolizumab vs CT) and IMvigor211 (atezolizumab vs CT)] RCTs. RESULTS: Overall, 3255 and 1452 patients were respectively included in the first- and second-line settings. In 1st line setting, compared with CT, no IO-based regimen exhibited survival benefit. However, all exclusive IO regimens resulted in lower rates of grade 3+ AEs. In 2nd line setting, compared with CT, only pembrolizumab improved OS benefit. Conversely, atezolizumab only showed OS benefit in exploratory analyses. Compared to second-line CT, no experimental regimen (atezolizumab or pembrolizumab) exhibited statistically significant ORR benefit. Both pembrolizumab and atezolizumab resulted in lower rates of grade 3+ AEs compared to 2nd line CT. CONCLUSIONS: In metastatic UC, IO-based regimens do not hold a survival benefit relative to CT in 1st line setting. However, pembrolizumab holds a survival benefit in 2nd line compared to CT. Several IO-based clinical trials are ongoing and will provide more and possibly better treatment alternatives for locally advanced and metastatic UC.

Immune-related adverse events as predictors of response in cancer patients undergoing immunotherapy. / Reacciones adversas inmunomediadas como predictoras de respuesta en pacientes oncológicos en tratamiento con inmunoterapia.

OBJECTIVE: To determine the incidence of immune-mediated adverse reactions with and without radiologic manifestations and to correlate them with the response to immunotherapy. MATERIAL AND METHODS: We retrospectively included 79 patients with stage IV lung carcinomas (n=24), renal carcinomas (n=11), or melanoma (n=44) treated with immunotherapy. We evaluated the occurrence of immune-mediated adverse reactions, their radiologic manifestations, and the response pattern according to the immune-related response criteria (irRC). We correlated the presence of immune-mediated adverse reactions with the response pattern. RESULTS: Immune-mediated adverse reactions occurred in 27.8%, being most common in patients with melanoma (40.9%). In 59.1% of patients with adverse reactions, there were radiologic manifestations such as pneumonitis, colitis, hypophysitis, thyroiditis, or myocarditis. Pneumonitis was the most common radiologic manifestation of immune-mediated adverse reactions, even in asymptomatic patients. The rate of response to immunotherapy was higher among patients who developed immune-mediated adverse reactions than in those who did not (68.2% vs. 38.6%, respectively, χ2 5.58; p=0.018). The rate of favorable responses was higher in patients with radiologic manifestations of immune-mediated adverse reactions than in those without radiologic manifestations (84.6% vs. 44.4%, respectively; p=0.023). CONCLUSIONS: The presence of immune-mediated adverse reactions is associated with a better response to immunotherapy. The association with a favorable response is even stronger in patients with radiologic manifestations of the immune-mediated adverse reactions.