Combo I-O plus chemotherapy

Chemotherapy has historically been considered immune-suppressive. The recent success of immune checkpoint inhibitors (ICI) has renewed interest in immunotherapies, and in combining them with chemotherapy to achieve additive or synergistic clinical activity [1,2].

Dr Luis Paz-Ares (Complutense University of Madrid, Spain) gave an overview about the combination of I-O and chemotherapy. The data of previous phase 1 studies evaluating front-line therapy of anti-PD-L1 or anti-PD1 agents in combination with chemotherapy were “not overwhelming”, Dr Paz-Ares mentioned [3]. “The response rates were in the range of 50%.” However, further research showed some more positive results. For example, the open-label Keynote-021 suggests that combination of pembrolizumab, carboplatin, and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC [4].

Subsequently, the Keynote-189 trial showed that in patients with previously untreated, metastatic, non-squamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer OS and PFS than chemotherapy alone (OS at 12 months: 69.2% vs 49.4%; HR for death 0.49; P<0.001). Improvement in OS was seen across all PD-L1 categories evaluated [5]. Comparable results were found in the Impower-132 trial, evaluating first-line combination of atezolizumab, carboplatin/cisplatin, and pemetrexed in stage 4 non-squamous NSCLC [6].

Potential implications

Dr Paz-Ares also provided insight into his current treatment decisions and possible policy in the future. “In most patients with high PD-L1 expression, I currently use immunotherapy. For patients with aggressive disease, with a high need for a quick symptomatic improvement, I would recommend chemo/I-O. For patients with moderate or low PD-L1 expression, chemo/I-O is preferred. Maybe in the future, but that is merely speculation, we are going to select patients based on TMB (see Table, his preferred options are shown in red).”

Table: Speculated treatment overview for patients selected on TMB



Options in red are preferred by Dr Paz-Ares.

1.  Emens LA, Middleton G. Cancer Immunol Res. 2015;3:436-43.
2. Galluzzi L, et al. Cancer Immunol Res. 2016;4:895-902.
3. Giaccone G, et al. Eur J Cancer 2015; 51(Suppl. 3): S107–S108.
4. Langer CJ, et al. Lancet Oncol. 2016;17:1497-1508.
5. Gandhi L, et al. N Engl J Med. 2018;378:2078-2092.
6. Papadimitrakopoulou VA, et al. WCLC 2018, abstract #OA05.07.

Posted on 25 June 201916 February 2024