96P Induction chemotherapy backbone in frail patients (pts) with advanced NSCLC treated with chemotherapy plus pembrolizumab (P): A single institution retrospective audit of dose intensities from modified regimens

Guidelines historically recommended mono-chemotherapy for the 1stline treatment of elderly/ECOG–PS 2 pts with NSCLC. Nowadays, there is no clear indication whether chemo-IO combinations can be effectively delivered in this population. We collected induction chemotherapy in pts with NSCLC treated with carboplatin (c) -based chemo-P regimens, to compute the received dose intensity (RDI) for standard (s) and modified (m) regimens due to age, comorbidities and PS. Comorbidities were stratified according to the comorbidity-polypharmacy score (CPS). The established cut-off of ≥85% for RDI was used to define adequate delivery. 116 pts were treated from Feb-20 to July-23, of whom 96 and 20 with non-squamous (nSq) and Sq histology, respectively treated with c-pemetrexed-P (CPem-P) and c-paclitaxel-P (CPac-P). The majority of pts were aged ≥70yo (52.6%), the median CPS was 5, with 58.6% having a CPS ≥5, whilst 47.4%, 44.8% and 7.8% had an ECOG-PS of 0, 1 and 2. PD-L1 TPS were <1% in 31.9% and 1-49% in 65.4%. Overall, 47.4% received a priori m-regimens due to PS, age, or comorbidities, although without pre-specified guidelines. Among pts with nSq-NSCLC, the absolute C and Pem received median doses were 1.37 AUC/week and 138.8 mg/smq/week, with a RDI of 86% and 75% (p<0.01) for pts treated with s- and m- regimens. Of note, the RDI was 57.9% among pts with ECOG-PS 2. However, pts treated with m-regimens experienced similar toxicities as those treated with s-regimens, despite being older (p<0.01), with higher PS (p<0.01) and more comorbid (p=0.03). Pts treated with m-regimens achieved a shorter survival (7.1 vs 13.9 months), which is comparable to IO-free historical controls. Among pts with nSq-NSCLC, 90% received m-regimens upfront, with absolute C and Pac median received doses of 1.19 AUC/week and 40 mg/smq/week, and an overall RDI of 73.5%. Although regimen modifications ensure a safe administration of chemo-P in frail pts, the RDI seems to be subtherapeutic, especially in those with Sq-NSCLC. Dedicated trials are needed to implement combination strategies in this population.