Discussion
TNBC, mTNBC, neutropenia
RECURRENT DISEASE, NEUTROPENIA
The combination of chemo-immunotherapy with PD-1/PD-L1 ICI became the standard of care for patients with PD-L1 positive advanced or mTNBC in 2019 following results from IMpassion130 and KEYNOTE-355 phase III trialsIn advanced TNBC, the combination of oleclumab plus durvalumab was evaluated in the BEGONIA trial (NCT03742102), a multi-cohort basket study testing various treatment combinations, including paclitaxel, durvalumab, and oleclumab. In the BEGONIA trial, the confirmed ORR was 45.5%, irrespective of PD-L1 statusAlso noteworthy is the fact that, as in the ALICE trial evaluating atezolizumab plus anthracycline-based chemotherapy in mTNBC, long-lasting responses were observed in patients with PD-L1 negative diseaseThe safety profile was consistent across the two arms and with data reported from other trials evaluating chemo-immunotherapy in advanced TNBC with similar rates of treatment discontinuation because of AEs. However, we noticed a slight increase in neutropenia in arm A, both in patients with de novo or recurrent disease without compromising chemotherapy exposure. Adenosine signaling and extracellular ATP are involved in neutrophil chemotaxis, and activation of adenosine receptors on neutrophils delays their apoptosisAlthough both arms were reasonably well balanced for baseline characteristics, there were a few imbalances, such as a lower proportion of patients with de novo mTNBC in arm A and a higher proportion of patients with recurrent disease previously exposed to carboplatin in arm B. Additional limitations of this study include that it was open-label, responses were investigator-assessed (rather than central-reviewed), and the study was not powered to assess a survival benefit. As a consequence of the interim analysis and the stop of accrual, the number of evaluable patients was limited. Therefore, all analyses outside of the primary endpoint are exploratory. As a result of the negative interim analysis, three patients from arm A, who had undergone maintenance immunotherapy for over a year, chose to stop taking oleclumab. The longer follow-up provides more data on the survival benefit of study treatments. Indeed, as observed with ICI use in routine, survival outcomes might be significantly improved despite a modest volumetric anti-tumoral responseIn our previous work, we showed that the expression of the adenosine-producing enzymes (CD39, CD73) was mainly observed in the mesenchymal stem-like subtype representing 15% of early TNBC and was associated with an immune margin-restricted subtype