Background: Pembrolizumab plus lenvatinib is a standard first-line treatment for metastatic renal cell carcinoma (mRCC) based on the phase III CLEAR trial. Real- world data are needed to assess effectiveness and toxicity management in routine practice. We report a retrospective single-institution experience and a case of grade 4 immune-related pancreatitis followed by sustained tumour control after treatment discontinuation. Methods: We retrospectively analysed consecutive patients with mRCC treated with first-line pembrolizumab plus lenvatinib at IRCCS Regina Elena from March 2024 through March 2026, with clinical follow-up updated through September 2026. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety outcomes, including dose modifications and permanent treatment discontinuations. Survival was estimated by the Kaplan–Meier method. Results: Thirty-eight patients were treated, and all were evaluable for response. ORR was 78.9% (4 complete responses and 26 partial responses). At a median follow- up of 11.7 months (95% CI 10.8–18.7), median PFS was not reached (95% CI 19.0–NR) and median OS was not reached (95% CI NR–NR). The estimated 12-month PFS and OS rates were 75.1% and 91.7%, respectively. Grade ≥3 adverse events occurred in 39.5% of patients. Lenvatinib was temporarily interrupted in 71.1% and dose-reduced in 60.5%. Permanent discontinuation due to toxicity occurred in 5.3% for lenvatinib and 15.8% for pembrolizumab; both agents were permanently discontinued in 2 (5.3%) patients. A representative case involved a 37-yearold woman who achieved an early partial response but developed grade 4 immune-related pancreatitis requiring high-dose corticosteroids (2 mg/kg) and second-line immunosuppression with mycophenolate mofetil and everolimus. Despite permanent discontinuation of both agents, partial response persisted at the August 2026 data cutoff. Conclusions: In this real-world cohort, pembrolizumab plus lenvatinib demonstrated high response rates and manageable toxicity consistent with pivotal trial data. Proactive dose modulation allowed treatment continuation in most patients, underscoring the importance of effective management of severe treatment-related toxicity in combination regimens to ensure optimal clinical outcomes in routine clinical settings. Download the Plain Language Summary of this article: https://www.drugsincontext.com/plain-language-summaries/plain-language-summary-pembrolizumab-plus-lenvatinib-in-first-line-metastatic-renal-cell-carcinoma-a-single-institution-experience-and-a-case-of-severe-treatment-related-toxicity-with-durable-tumour This article is part of the Special Issue From evidence to the individual patient: pembrolizumab plus lenvatinib in real-world metastatic renal cell carcinoma: https://www.drugsincontext.com/special_issues/from-evidence-to-the-individual-patient-pembrolizumab-plus-lenvatinib-in-real-world-metastatic-renal-cell-carcinoma
We report the case of a 65-year-old woman diagnosed with metastatic chromophobe renal cell carcinoma, classified as intermediate risk according to IMDC criteria, who presented with a large left renal mass, para-aortic lymphadenopathy and bilateral pulmonary nodules. First-line treatment with pembrolizumab plus lenvatinib achieved a rapid partial response associated with prolonged distant disease control, with significant symptomatic improvement and recovery of daily functioning. Treatment-related toxicities required lenvatinib dose reduction, allowing continued therapy with good tolerability. After approximately 1 year of treatment, isolated local progression of the primary tumour occurred, while metastatic sites remained controlled. Following multidisciplinary evaluation, the patient underwent deferred cytoreductive radical nephrectomy. This case highlights the potential role of immunotherapy–tyrosine kinase inhibitor combinations in rare renal cell carcinoma subtypes, underscores the value of personalized multimodal strategies, including deferred surgery, and emphasizes the importance of proactive toxicity management to preserve long-term treatment benefit and quality of life. Download the Plain Language Summary of this article: https://www.drugsincontext.com/plain-language-summaries/plain-language-summary-pembrolizumab-plus-lenvatinib-enabling-cytoreductive-nephrectomyin-metastatic-chromophobe-renal-cell-carcinoma-a-case-report This article is part of the Special Issue From evidence to the individual patient: pembrolizumab plus lenvatinib in realworld metastatic renal cell carcinoma: https://www.drugsincontext.com/special_issues/from-evidence-to-the-individual-patient-pembrolizumab-plus-lenvatinib-in-real-world-metastatic-renal-cell-carcinoma
Immune-checkpoint inhibitors have reshaped the therapeutic armamentarium of advanced renal cell carcinoma while increasing the incidence of immune-related adverse events. Among these, bullous dermatoses are rare but potentially severe and therapeutically challenging. We report a case of pemphigoid-like dermatosis induced by pembrolizumab and lenvatinib in a patient affected by metastatic renal cell carcinoma. Initial management with systemic corticosteroids led to complete clinical remission; however, early relapse with vesiculobullous erythema required treatment escalation with the introduction of dupilumab. We discuss the underlying immunopathogenesis, differential diagnosis and multidisciplinary management strategies in accordance with current international guidelines and the literature. We also highlight the feasibility of effectively managing treatment-related cutaneous toxicity with dupilumab, allowing continuation of oncological therapy without compromising disease control. Multidisciplinary, tailoredpatient treatment workups remain the gold standard for the management of these toxicities. Download the Plain Language Summary of this article: https://www.drugsincontext.com/plain-language-summaries/plain-language-summary-pembrolizumab-and-lenvatinib-associated-pemphigoid-like-dermatosis-in-advanced-renal-cell-carcinoma-the-hidden-cost-of-synergy-successfully-managed-with-dupilumab This article is part of the Special Issue From evidence to the individual patient: pembrolizumab plus lenvatinib in real-world metastatic renal cell carcinoma: https://www.drugsincontext.com/special_issues/from-evidence-to-the-individual-patient-pembrolizumab-plus-lenvatinib-in-real-world-metastatic-renal-cell-carcinoma
Metastatic renal cell carcinoma (mRCC) presents with marked biological heterogeneity, and bone involvement is associated with aggressive disease and limited response to systemic therapies. We report the case of a 33-year-old female patient with clear cell mRCC who developed metastatic progression after undergoing curative-intent surgery, presenting with vertebral bone metastasis at C7 and peritoneal carcinomatosis. First-line treatment with pembrolizumab plus lenvatinib was initiated, leading to a deep and durable response. A radiological complete response was achieved at all metastatic sites, and subsequent surgery confirmed histological complete remission in the bone lesion. Pathologically documented complete responses in bone metastases from RCC are remarkably rare. This case highlights the potential of immune-checkpoint inhibitor–tyrosine kinase inhibitor combinations to induce profound responses even in unfavourable metastatic patterns and supports a multidisciplinary treatment strategy. Download the Plain Language Summary of this article: https://www.drugsincontext.com/plain-language-summaries/plain-language-summary-complete-pathological-response-of-bone-metastasis-in-metastatic-renal-cell-carcinoma-treated-with-pembrolizumab-plus-lenvatinib-after-surgical-debulking-and-palliative-radio This article is part of the Special Issue From evidence to the individual patient: pembrolizumab plus lenvatinib in real-world metastatic renal cell carcinoma: https://www.drugsincontext.com/special_issues/from-evidence-to-the-individual-patient-pembrolizumab-plus-lenvatinib-in-real-world-metastatic-renal-cell-carcinoma
This Editorial introduces a collection of five case reports exploring the management of metastatic renal cell carcinoma in real-world clinical practice, with particular attention to the use of pembrolizumab plus lenvatinib across diverse and challenging clinical scenarios. Drawing on the cases presented in the collection, the Editorial discusses key considerations in treatment selection, including histology, disease burden and metastatic pattern, treatment goals, toxicity management and the integration of systemic and locoregional approaches. Particular attention is given to uncommon or aggressive disease presentations, treatment-related toxicities, histological reassessment and therapeutic sequencing. These cases provide clinically relevant insights into individualized decision-making but remain hypothesis-generating and should be interpreted within the broader evidence from prospective trials and real-world studies. This article is part of the Special Issue From evidence to the individual patient: pembrolizumab plus lenvatinib in real-world metastatic renal cell carcinoma: https://www.drugsincontext.com/special_issues/from-evidence-to-the-individual-patient-pembrolizumab-plus-lenvatinib-in-real-world-metastatic-renal-cell-carcinoma
