Abstract 66P
Background
Apart from PD-L1 expression, no predictors for choosing between Pembrolizumab (Pembro) or Pembrolizumab-chemotherapy (Pembro-CT) as frontline treatment for advanced NSCLC are validated. Here we explore the potential role of different clinical, radiological, biological factors.
Methods
We retrospectively collected data from 112 and 84 patients, selected for Pembro or Pembro-CT solely based on PD-L1 as per Italian prescribing limitation (combination treatment reserved to PD-L1<50%), at two health facilities, and evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR).
Results
Median follow-up was 12.5 and 10.4 months for Pembro and Pembro-CT groups, respectively. The multiple analyzed sub-groups and their OS data are reported in table. Among females, we found a statistical difference (p = 0.01) in PFS, but not in OS, favoring Pembro-CT over Pembro, although median OS in the former sub-group was not reached (NR). Among patients harboring any KRAS mutations, we observed an advantage of Pembro-CT over Pembro in terms of PFS (p = 0.02), with a trend of benefit in OS. In the Pembro group, patients harboring KRAS wild type tumors achieved longer PFS than patients harboring KRAS mutant tumors (p = 0.04). No statistical difference was found in ORR (p = 0.87) nor DCR (p = 0.07) among the sub-groups. However, a higher number of early deaths occurred in the Pembro compared to Pembro-CT group (6 vs. 13).
Table: 66P| Pembro | Pembro-CT | P | |
|---|---|---|---|
| OS (m) | 14.4 | 13.4 | 0.6 |
| Male | 16.5 | 12.6 | 0.09 |
| Female | 20.3 | NR | 0.32 |
| Non squamous | 20.3 | 12.6 | 0.41 |
| Squamous | 15.5 | 13.4 | 0.6 |
| Never smokers | 23.3 | 12.6 | 0.44 |
| Age>70 | 16.0 | 12.5 | 0.35 |
| PS ECOG≥2 | 2.5 | 1.5 | 0.34 |
| KRAS mutant | 9.7 | 16.0 | 0.33 |
| Tumor burden>62 mm | 10.9 | 10.9 | 0.91 |
| N# lesions >3 | 13.9 | 10.9 | 0.32 |
| Brain metastases | 8.7 | 9.0 | 0.6 |
| LIPI intermediate | 20.3 | 16.0 | 0.8 |
| Poor | 5.9 | 5.5 | 0.64 |
| Corticosteroids>10 mg/day | 2.7 | 8.6 | 0.38 |
| Proton pump inhibitors | 9.2 | 10.4 | 0.93 |
Conclusions
While no significant differences were found in OS, some patients, notably those harboring KRAS alterations, may benefit from the addition of chemotherapy. The enrichment of Pembro-CT group, together with molecular data revealing potential co-mutations, would provide more robust findings.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. Barletta: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Pierre Fabre, GlaxoSmithKline, Bristol-Myers Squibb. C. Dellepiane: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche. G. Rossi: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen, Roche. E. Bennicelli: Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb. L. Cantini: Financial Interests, Personal, Stocks/Shares, stock and/or other ownership interests: Labcorp Drug Development. L. Del Mastro: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Pfizer, Merck Sharp & Dohme, Genomic Health, Takeda, Ipsen, Eisai, Eli Lilly, Celgene, Pierre Fabre, Seagen, Daiichi Sankyo, Exact Sciences, Amgen. R. Berardi: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Novartis, Merck, Otsuka, Eli Lilly, Roche. C. Genova: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Roche, Sanofi, Takeda, ThermoFisher. All other authors have declared no conflicts of interest.