Background
The effect of the sequential combination of chemotherapy and immune checkpoint inhibitors (ICIs) remains unclear. Here, we evaluated the efficacy of different chemotherapy regimens administered after ICIs in advanced non‐small cell lung cancer (NSCLC), compared to the same regimens administered without previous ICIs.
Methods
We retrospectively included all patients treated between 2015 and 2019 for an advanced NSCLC, receiving a salvage chemotherapy just after ICI (CAI group) comparing them to ICI naive patients (CWPI group) undergoing the same chemotherapy at Bordeaux University Hospital. The primary outcome was the time to treatment discontinuation (TTD), and secondary endpoints were overall survival (OS) and overall response rate (ORR).
Results
A total of 152 patients were included, with 34/23 (CAI/CWPI) receiving paclitaxel/bevacizumab (PB), 24/11 paclitaxel (P), 27/12 gemcitabine (G) and 6/15 pemetrexed (PE). Characteristics were comparable, except for CAI treated with PB (more patients with an ECOG PS ≤1 [p <0.001]). Median number of lines received was higher in CAI for all groups. There was no difference between CAI and CWPI for TTD, OS and ORR. However, PB was associated with a nonsignificant increase in OS in the CAI group (HR = 0.65; 95% CI: 0.38–1.2, p = 0.17].
Conclusion
Our data showed no difference in TTD, OS and ORR regardless of chemotherapy, but a trend towards an increased OS with PB when given after an ICI, while patients received chemotherapy later in the CAI group. This suggests that a sequential combination of ICI followed by chemotherapy could be an interesting strategy in advanced NSCLC for selected patients.
Clear cell renal cell carcinoma (RCC) oncogenesis is mainly driven by VHL gene inactivation, leading to overexpression of vascular endothelial growth factor (VEGF). The use of tyrosine-kinase inhibitors (TKIs) directed against VEGF and its receptor (VEGFR) revolutionised the management of metastatic renal cancer in the 2000s. The more recent development of next-generation TKIs such as cabozantinib or lenvatinib has made it possible to bypass some of the mechanisms of resistance to first-generation anti-VEGFR TKIs. During the decade 2010–2020, the development of immune checkpoint blockade (ICB) therapies revolutionised the management of many solid cancers, including RCC, in first- and subsequent-line settings. Dual ICB or ICB plus anti-VEGFR TKI combinations are now the standard of care for patients with advanced clear cell RCC. To optimise these combination therapies while preserving patient quality of life, escalation and de-escalation strategies are being evaluated in prospective randomised trials, based on patient selection according to their prognosis risk. Finally, new therapeutic approaches, such as targeting hypoxia-inducible factor (HIF) and the development of innovative treatments using antibody-drug conjugates (ADCs), CAR-T cells, or radiopharmaceuticals, are all potential candidates to improve further patient survival.
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