PD-L1 ≥ 50% Lung Cancer Refractory to PD-1 Inhibition: The Role of Salvage Chemo-Immunotherapy Combination

Abstract

Novel treatment strategies incorporating PD-1/PD-L1 inhibitors in the first-line setting of advanced non-small-cell lung cancer (NSCLC) provided relevant improvements in survival outcomes. Among NSCLC patients with PD-L1 tumor proportion score ≥50%, identifying the ones to be addressed to pembrolizumab monotherapy or chemo-immunotherapy combinations is a matter of debate, taking into account the risks of overtreatment and toxicity. Here we report the clinical stories of four NSCLC patients with PD-L1 tumor proportion score ≥50% and good performance status, sharing high tumor burden including serosal involvement. After having rapidly progressed on first-line PD-1/PD-L1 inhibitors, they achieved major clinical and radiological response to pembrolizumab-chemotherapy combination. These cases prove the feasibility and effectiveness of salvage chemo-immunotherapy in pembrolizumab-refractory NSCLC patients.

Lay abstract

Although chemotherapy is still the pillar of lung cancer treatment, immunotherapy agents (i.e., drugs that foster the immune system against the tumor) have revolutionized the care of patients suffering from lung malignancies. Depending on the type of lung cancer and specific characteristics of tumor cells (i.e., the expression of a protein called PD-L1), the first treatment of choice can be either the immunotherapy alone or a combination of chemotherapy and immunotherapy agents. In this article, we report the clinical histories of four patients who received immunotherapy alone as the first treatment. Unfortunately, their disease rapidly progressed. Albeit the second-line treatment should have been chemotherapy only, immunotherapy was maintained together with chemotherapy. All the four patients then experienced remarkable benefit from the combination of chemotherapy and immunotherapy, and the degree of the disease responses obtained suggest it relied not only on chemotherapy, but on the synergistic effect of maintaining immunotherapy.

Keywords::

• disease burden
• early evaluation
• first-line
• non-small-cell lung cancer
• NSCLC
• PD-L1 expression
• pembrolizumab
• primary resistance
• progression

Financial & competing interests disclosure

Francesco Facchinetti declares having attended editorial activities sponsored by Roche and BMS. Marcello Tiseo declares advisory boards and speakers’ fees from AstraZeneca, Pfizer, Eli Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre; research grants from AstraZeneca and Boehringer Ingelheim. Andrea Ardizzoni reports receipt of grants and personal fees from BMS, personal fees from MSD, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Pfizer, and grants from Celgene outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

Francesco Facchinetti declares having attended editorial activities sponsored by Roche and BMS. Marcello Tiseo declares advisory boards and speakers’ fees from AstraZeneca, Pfizer, Eli Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre; research grants from AstraZeneca and Boehringer Ingelheim. Andrea Ardizzoni reports receipt of grants and personal fees from BMS, personal fees from MSD, personal fees from Eli Lilly, personal fees from Boehringer, personal fees from Pfizer, and grants from Celgene outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.