- Late stage patients with less than 50% PD(L)-1 have several options depending on histology.
- Nivolumab plus ipilimumab may produce critically misleading imaging in the neoadjuvant setting.
Why this matters
- Different accepted protocols allow better treatment personalisation.
- Radiologists needs to be aware of nodal immune flares.
Stage IV NSCLC setting:
For patients with PD-L1 staining of ≥50%, the front-line single agent PD-(L)1 inhibitor therapy based on pembrolizumab provides an overall survival of 20-30 months and is an established first-line option. Front-line atezolizumab provides an overall survival of 20 months in TC3/IC3 patients and may become a treatment option in the future.
Front-line chemoimmunotherapy (chemotherapy plus PD-(L)1 inhibitors ± anti-angiogenics) is now standard treatment for patients without PD(L)-1 contraindications and with less than 50% PD(L)-1. It can be also be an option for those with more than 50% PD(L)-1, particularly with rapidly progressive disease.
For the squamous NSCLC type, the standard front-line treatment is carboplatin, a taxane, and pembrolizumab. For non-squamous NSCLC: a platinum, pemetrexed, and pembrolizumab OR carboplatin and atezolizumab plus nab-paclitaxel or bevacizumab plus paclitaxel are used.
Regarding immunotherapy combinations, nivolumab and ipilimumab in PD(L)-1 negative patients (less than 1%) could be beneficial but this data is lacking and dependent on future studies.
Nivolumab plus ipilimumab is effective but it may cause nodal immune flares (NIFs): apparent radiographic nodal progression with pathologic examination revealing granulomas but no tumour. It is important to distinguish NIF from disease progression which may wrongly cause patients to be deemed ineligible for potentially curative surgery.