Efficacité de la combinaison paclitaxel hebdomadaire-bevacizumab pour les patients avec un cancer bronchopulmonaire non à petites cellules non épidermoïdes (CBNPC) : AVATAX, une étude rétrospective multicentrique

Introduction: With the growing role of immunotherapy (ICI) as first-line setting for advanced NSCLC, strategies must be redefined after failure. The combination paclitaxel-bevacizumab showed in the ULTIMATE trial a significant superiority versus docetaxel as second or third-line treatment. Limited retropective studies have demonstrated unexpected efficacy of chemotherapy after prior progression on ICI. This combination could be used as salvage treatment following ICI. Methods: This multi-centric retrospective study identified patients treated with the combination paclitaxel- bevacizumab in metastatic non-squamous NSCLC as second-line therapy or beyond. Main objectives were to describe safety and efficacy of this combination, with a special attention to the sub-group treated just after ICI. Results: From January 2010 to February 2020, 314 patients started the paclitaxel-bevacizumab combination: 55% male, with a median age of 60 years, 27% with a performance status ≥2, 45% with brain metastases. A majority of patients were treated in second (20%) and third-line (39%), and 28% were treated just after ICI failure (88/314). Objective response rate (ORR) was 40% and disease control rate was 77 %. Median progression-free survival (PFS) and overall survival (OS) were 5,7 months [IQ,3,2–9,6] and 10,8 months [IQ,5,3–19,6] respectively. All grade adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued a monotherapy alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compared to those not previously treated with ICI (ICI-): 7,0 months [IQ,4,2–11,0] vs 5,2 months [IQ,2,9–8,8] p (log-rank)=0,01. There was no statistically significant difference in terms of OS between these two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment (ICI+) and performance status. Conclusion: This study confirms an acceptable toxicity profile associated with interesting efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non–squamous NSCLC patients, particularly after progression with ICI.Introduction : L'utilisation de l’immunothérapie en première ligne de traitement des CBNPC de stade avancé nécessite de redéfinir les lignes ultérieures. La combinaison paclitaxel-bevacizumab avait montré son efficacité dans l’essai ULTIMATE en seconde et troisième ligne. AVATAX est une étude française évaluant cette combinaison en vie réelle. Méthodes : Il s’agit d’une étude rétrospective multicentrique. L’objectif principal était d’évaluer la tolérance et l’efficacité de l’association paclitaxel-bevacizumab pour les CBNPC non épidermoïdes en seconde ligne et plus, avec un intérêt plus particulier pour le sous-groupe des patients traités juste après progression sous inhibiteurs des points de contrôle immunitaire (ICI). Résultats : Entre janvier 2010 et février 2020, 314 patients ont débuté la combinaison : 55% d'hommes, avec âge médian au diagnostic de 60 ans, 27% avaient un statut PS≥2, 45% avec des métastases cérébrales. Une majorité de patients étaient traités en deuxième (20%) et en troisième (39%) ligne et 28% avaient reçu un ICI à la ligne précédente. Le nombre de cures médian a été de 4 [interquartiles (IQ) [3-6]. Le taux de réponse objective était de 40% et le taux de contrôle de la maladie de 77%. Les médianes de survie sans progression (SSP) et de survie globale (SG) étaient de 5,7 mois [IQ,3,2–9,6] et 10,8 mois [IQ,5,3–19,6] respectivement. Les effets secondaires tous grades confondus ont concerné 82% des patients : 53% d’asthénie et 39% de neurotoxicité. La combinaison est devenue une monothérapie pour 25% des patients en raison de toxicité. La SSP médiane des patients traités juste après ICI était significativement supérieure par rapport à celle des patients non préalablement traités par ICI : 7,0 mois [IQ,4,2–11,0] vs 5,2 mois [IQ,2,9–8,8] p (log-rank)=0,01. En revanche, il n’y avait pas de différence significative en termes de SG médiane entre ces 2 groupes. En analyse multivariée, les facteurs associés à une meilleure SSP étaient un traitement par ICI la ligne précédente et l’indice de performance. Seul l’indice de performance était associé à la SG. Conclusion : Ces données confirment en vie réelle les résultats d'efficacité et de tolérance de l'essai ULTIMATE. La combinaison paclitaxel-bevacizumab est particulièrement efficace après progression sous ICI

COVID-19 in breast cancer patients: A cohort at the Institut Curie hospitals in the Paris area

International audienceBackground: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). Methods: An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities. Results: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death. Conclusions: This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients