REchallenge of NIVOlumab (RENIVO) or Nivolumab-Ipilimumab in Metastatic Renal Cell Carcinoma: An Ambispective Multicenter Study

Charles Vauchier; Edouard Auclin; Philippe Barthélémy; Lucia Carril-Ajuria; Thomas Ryckewaert; Delphine Borchiellini; Zahra Castel-Ajgal; Mostefa Bennamoun; Luca Campedel; Antoine Thiery-Vuillemin; Elodie Coquan; Laurence Crouzet; Jean-François Berdah; Christine Chevreau; Raffaele Ratta; Aude Fléchon; Felix Lefort; Laurence Albiges; Marine Gross-Goupil; Yann-Alexandre Vano; Constance Thibault; Stéphane Oudard

doi:10.1155/2022/3449660

REchallenge of NIVOlumab (RENIVO) or Nivolumab-Ipilimumab in Metastatic Renal Cell Carcinoma: An Ambispective Multicenter Study

J Oncol. 2022 Feb 18:2022:3449660. doi: 10.1155/2022/3449660. eCollection 2022.

Authors

Charles Vauchier¹, Edouard Auclin¹, Philippe Barthélémy², Lucia Carril-Ajuria³, Thomas Ryckewaert⁴, Delphine Borchiellini⁵, Zahra Castel-Ajgal⁶, Mostefa Bennamoun⁷, Luca Campedel⁸, Antoine Thiery-Vuillemin⁹, Elodie Coquan¹⁰, Laurence Crouzet¹¹, Jean-François Berdah¹², Christine Chevreau¹³, Raffaele Ratta¹⁴, Aude Fléchon¹⁵, Felix Lefort¹⁶, Laurence Albiges³, Marine Gross-Goupil¹⁶, Yann-Alexandre Vano^{1

17}, Constance Thibault¹, Stéphane Oudard^{1

18}

Affiliations

¹ Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, Université de Paris, Paris 75015, France.
² Medical Oncology Unit, Institut de Cancérologie Strasbourg Europe, Strasbourg 67200, France.
³ Oncology Department, Institut Gustave Roussy, Université Paris-Saclay, Villejuif 94076, France.
⁴ Department of Medical Oncology, Centre Oscar Lambret, Lille 59000, France.
⁵ Department of Medical Oncology, Centre Antoine-Lacassagne, Université Côte d'Azur, Nice 06100, France.
⁶ Medical Oncology Department, Hôpital Cochin-Port Royal, AP-HP, Paris75014, France.
⁷ Department of Medical Oncology, Institut Mutualiste Montsouris, Paris 75014, France.
⁸ Department of Oncology, Hôpital Pitié Salpêtrière, AP-HP, Paris 75013, France.
⁹ Department of Medical Oncology, Centre Hospitalier Universitaire de Besançon, Besançon 25000, France.
¹⁰ Medical Oncology Department, Centre François Baclesse, Caen 14000, France.
¹¹ Oncology Department, Centre Eugène Marquis, Rennes 35000, France.
¹² Oncology Department, Clinique Sainte-Marguerite, Hyères 83400, France.
¹³ Department of Medical Oncology, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse 31100, France.
¹⁴ Oncology and Supportive Care Department, Hôpital Foch, Suresnes 92150, France.
¹⁵ Department of Medical Oncology, Centre Léon Bérard, Lyon 69008, France.
¹⁶ Department of Medical Oncology, Centre Hospitalier Universitaire de Bordeaux-Hôpital Saint-André, Bordeaux 33000, France.
¹⁷ Centre de Recherche des Cordeliers, INSERM, Université de Paris, Sorbonne Université, Paris 75006, France.
¹⁸ Université de Paris, PARCC, INSERM U970, Paris 75006, France.

Abstract

Introduction: Immune checkpoint inhibitors (ICI) have been approved for front-line therapy in metastatic renal cell carcinoma (mRCC). However, progressive disease often occurs and subsequent therapies are needed. ICI rechallenge may be an option, but there is a lack of data regarding efficacy and prognostic factors. We assessed efficacy of ICI rechallenge and factors associated with better outcomes. Patients and Methods. This ambispective multicenter study included 45 mRCC patients rechallenged with nivolumab ± ipilimumab between 2014 and 2020. Primary endpoint was investigator-assessed best objective response rate (ORR) for ICI rechallenge (ICI-2). Factors associated with ICI-2 progression-free survival (PFS) were evaluated with multivariate Cox models.

Results: ORR was 51% (n = 23) at first ICI therapy (ICI-1) and 16% (n = 7) for ICI-2. Median PFS was 11.4 months (95% CI, 9.8-23.5) and 3.5 months (95% CI, 2.8-9.7), and median overall survival was not reached (NR) (95% CI, 37.8-NR) and 24 months (95% CI, 9.9-NR) for ICI-1 and ICI-2, respectively. Factors associated with poorer ICI-2 PFS were a high number of metastatic sites, presence of liver metastases, use of an intervening treatment between ICI regimens, Eastern Cooperative Oncology Group performance status ≥2, and poor International Metastatic RCC Database Consortium score at ICI-2 start. Conversely, ICI-1 PFS >6 months was associated with better ICI-2 PFS. In multivariate analysis, there were only statistical trends toward better ICI-2 PFS in patients with ICI-1 PFS >6 months (p=0.07) and toward poorer ICI-2 PFS in patients who received a treatment between ICI regimens (p=0.07).

Conclusion: Rechallenge with nivolumab-based ICI has some efficacy in mRCC. We identified various prognostic factors in univariate analysis but only statistical trends in multivariate analysis. Our findings bring new evidence on ICI rechallenge and preliminary but unique data that may help clinicians to select patients who will benefit from this strategy.