Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response

Loibl, Sibylle; Schneeweiß, Andreas; Huober, Jens; Braun, Michael; Rey, Julia; Blohmer, Jens-Uwe; Furlanetto, Jenny; Zahm, Dirk M.; Hanusch, Claus; Thomalla, Jörg; Jackisch, Christian; Staib, Peter; Link, Theresa; Rhiem, Kerstin; Solbach, Christine; Fasching, Peter A.; Nekljudova, Valentina; Denkert, Carsten; Untch, Michael

doi:10.1016/j.annonc.2022.07.1940

Cited by 88 publications

(85 citation statements)

References 26 publications

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“…This study included four different randomized controlled trials. The addition of the ICI to NAC increased the survival of TNBC regardless of the PD-L-1 status of the tumors, which is in line with many other recent studies that showed the positive benefit of adding immunotherapies with traditional NAC for the treatment of early TNBC ( 13 , 14 ). In support of the latter, Pembrolizumab has been approved by the FDA along with NAC for the treatment of high-risk early-stage TNBC ( 15 ).…”

Section: Introductionsupporting

confidence: 87%

Editorial: Recent advancements in neoadjuvant chemotherapy for specific breast cancer subtypes

et al. 2022

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Section: Introductionsupporting

confidence: 87%

Editorial: Recent advancements in neoadjuvant chemotherapy for specific breast cancer subtypes

et al. 2022

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“…In contrast with positive clinical trials (I-SPY2, Impassion031, KEYNOTE-522), 12 , 15 , 55 , 56 the phase II GeparNuevo, randomizing patients to receive nab-paclitaxel followed by dose dense anthracyclines and cyclophosphamide with either durvalumab or placebo, failed to demonstrate a statistically significant improvement in the primary endpoint of pCR (53.4% versus 44.2%, OR: 1.45) but showed potential clinical benefit after 42 months of follow-up in a descriptive analysis, in terms of 3-year invasive disease-free survival (iDFS, 84.9% versus 76.9%; HR 0.54, 95% CI 0.27–1.09), 3-year distant disease-free survival (DDFS, 91.4% versus 79.5%; HR 0.37, 95% CI 0.15–0.87) and 3-year OS (95.1% versus 83.1%, HR 0.26, 95% CI 0.09–0.79). 57 , 58 Unlike the other three similar positive trials, which enrolled only patients with stage II–III TNBC, 35% of patients from GeparNuevo had a TNBC in stage I and seemed to derive a lower benefit in terms of pCR from the addition of durvalumab. Although the study was formally negative for its primary endpoint, the significant difference found in iDFS represents an intriguing finding, suggesting that pCR may be not the sole driver of IO benefit in early TNBC, and that clinical outcomes may also be independent of pCR, especially when investigating IO agents.…”

Section: Challenges Of Immunotherapy For Early-stage Tnbcmentioning

confidence: 99%

“…Contrarily, the 3-year EFS rate of patients enrolled in KEYNOTE-522 who reached the pCR (94.4% versus 92.5%, HR: 0.73, 95% CI: 0.39–0.36) suggests the exploration of de-intensification strategies to spare post-neoadjuvant pembrolizumab and, consequently, clinical, psychological, and financial toxicities; this hypothesis is corroborated by GeparNuevo trial, which demonstrated an underpowered but significant OS benefit and did not include post-neoadjuvant durvalumab. 15 , 58 …”

Section: Challenges Of Immunotherapy For Early-stage Tnbcmentioning

confidence: 99%

“…First, the choice of the best backbone chemotherapy is not fully understood, in particular platinum salts demonstrated to provide an EFS benefit when added to standard NACT but GeparNuevo trial showed a survival benefit also without carboplatin 58 , 91 ; therefore, the need for platinum in the presence of pembrolizumab has to be assessed. Furthermore, KEYNOTE-522 did not include dose-dense anthracyclines and cyclophosphamide (AC) regimen, which has demonstrated to be superior to standard AC 92 ; hence, also the role of dose dense AC in association to ICIs needs to be clarified.…”

Section: Challenges Of Immunotherapy For Early-stage Tnbcmentioning

confidence: 99%

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Evolving treatment landscape of immunotherapy in breast cancer: current issues and future perspectives

et al. 2023

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Immune checkpoint inhibitors (ICIs) deeply changed the treatment landscape of breast cancer (BC). In particular, anti-programmed-death (ligand) 1 antibodies were approved for the treatment of triple-negative breast cancer (TNBC), both in first line for metastatic disease and in neoadjuvant setting, on the basis of a demonstrated improvement of the survival outcomes. In light of these results, current clinical trials aim at improving this benefit investigating novel combinations and strategies, at exploring the role of ICIs beyond TNBC, and at better selecting the patients in order to spare non-responders from avoidable toxicities. This narrative review aims at summarizing and discussing the evolving landscape of immunotherapeutic treatments for BC, highlighting the current challenges and the future perspectives.

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“…In summary, ICIs exert antitumor effects by modulating the body’s immune system instead of killing tumor cells directly. In accumulating studies, durable tumor control was achieved with better effects than traditional chemotherapy and/or radiotherapy ( 95 – 98 ). This unique mechanism provided the rationale for neoadjuvant immunotherapy, whereby long-term survival is expected.…”

Section: Rationale Of Neoadjuvant Therapymentioning

confidence: 99%

Neoadjuvant immunotherapy for resectable esophageal cancer: A review

Liu

Ding

2022

Front. Immunol.

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Esophageal cancer (EC) is one of the most common cancers worldwide, especially in China. Despite therapeutic advances, the 5-year survival rate of EC is still dismal. For patients with resectable disease, neoadjuvant chemoradiotherapy (nCRT) in combination with esophagectomy is the mainstay of treatment. However, the pathological complete response (pCR) rate to nCRT of 29.2% to 43.2% is not satisfactory, and approximately half of the patients will develop either a locoregional recurrence or distant metastasis. It is, therefore, necessary to explore novel and effective treatment strategies to improve the clinical efficacy of treatment. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) has significantly changed the treatment paradigm for a wide variety of advanced cancers, including EC. More recently, increasing clinical evidence has demonstrated that neoadjuvant immunotherapy can potentially improve the survival of patients with resectable cancers. Furthermore, accumulating findings support the idea that chemotherapy and/or radiotherapy can activate the immune system through a variety of mechanisms, so a combination of chemotherapy and/or radiotherapy with immunotherapy can have a synergistic antitumor effect. Therefore, it is reasonable to evaluate the role of neoadjuvant immunotherapy for patients with surgically resectable EC. In this review, we discuss the rationale for neoadjuvant immunotherapy in patients with EC, summarize the current results of utilizing this strategy, review the planned and ongoing studies, and highlight the challenges and future research needs.

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Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response

Cited by 88 publications

References 26 publications

Editorial: Recent advancements in neoadjuvant chemotherapy for specific breast cancer subtypes

Editorial: Recent advancements in neoadjuvant chemotherapy for specific breast cancer subtypes

Evolving treatment landscape of immunotherapy in breast cancer: current issues and future perspectives

Neoadjuvant immunotherapy for resectable esophageal cancer: A review

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