Atezolizumab in combination with carboplatin + etoposide for heavily treated small cell lung cancer
- 3 years ago
Thorac Cancer. 2020 Sep; 11(9): 2740–2742. doi: 10.1111/1759-7714.13588
A 60‐year‐old male extensive‐stage small cell lung cancer (ES‐SCLC) patient had been previously diagnosed (cT4N3M1a [PUL], stage VIA) 35 months before the start of this study, and had been treated with the following regimens and response evaluations: carboplatin and etoposide (CE) for four cycles with a partial response (PR) and a time to progression (TTP) of nine months, carboplatin and etoposide (CE) rechallenge as a sensitive relapse for four cycles with stable disease (SD) and a TTP of nine months, amrubicin for six cycles with SD, and a TTP of six months with brain metastasis as a progressive disease (PD) site treated using stereotactic radiosurgery (SRS), irinotecan for six cycles with SD and a TTP of six months, and carboplatin and etoposide (CE) rechallenge for the third time administration for two cycles with PD and a TTP of two months.
After three months of treatment holiday following PD with third time CE, atezolizumab and carboplatin and etoposide (CE) were administered, which resulted in a PR after three cycles at the primary site (Fig (Fig1)1) and in SD with a limited tumor shrinkage of brain metastasis (Fig (Fig2).2). After four cycles of induction treatment, atezolizumab continuation maintenance therapy was followed for two cycles, and the response remained durable for five months with an ongoing regimen without any immune‐related adverse events.
Atezolizumab was the first immune checkpoint inhibitor (ICI) to be introduced as a first‐line treatment option for extensive‐stage small cell lung cancer (ES‐SCLC), in combination with carboplatin and etoposide (CE) chemotherapy. However, SCLC treatment options after progression to first‐line chemotherapy are limited, warranting the readministration of previously used drugs. In combination with atezolizumab, CE readministration may theoretically be effective, based on two tentative mechanisms: its additive and synergistic effects on cytotoxic chemotherapy. The additive effect is based on the IFCT‐1603 trial in which the Kaplan‐Meier estimates of both progression‐free survival (PFS) and overall survival (OS) in the atezolizumab group exhibited a tail plateau in the selected population. Conversely, an anti‐PD‐L1 antibody synergistic effect on platinum compounds was assessed in a preclinical study, which was reinforced by clinical data. Thus, atezolizumab in combination with CE may be a treatment option in heavily treated patients. Here, we describe the first case of a heavily treated ES‐SCLC patient treated with chemoimmunotherapy, resulting in a partial response and a durable PFS.
A 60‐year‐old male extensive‐stage small cell lung cancer (ES‐SCLC) patient had been previously diagnosed (cT4N3M1a [PUL], stage VIA) 35 months before the start of this study, and had been treated with the following regimens and response evaluations: carboplatin and etoposide (CE) for four cycles with a partial response (PR) and a time to progression (TTP) of nine months, carboplatin and etoposide (CE) rechallenge as a sensitive relapse for four cycles with stable disease (SD) and a TTP of nine months, amrubicin for six cycles with SD, and a TTP of six months with brain metastasis as a progressive disease (PD) site treated using stereotactic radiosurgery (SRS), irinotecan for six cycles with SD and a TTP of six months, and carboplatin and etoposide (CE) rechallenge for the third time administration for two cycles with PD and a TTP of two months.
After three months of treatment holiday following PD with third time CE, atezolizumab and carboplatin and etoposide (CE) were administered, which resulted in a PR after three cycles at the primary site (Fig (Fig1)1) and in SD with a limited tumor shrinkage of brain metastasis (Fig (Fig2).2). After four cycles of induction treatment, atezolizumab continuation maintenance therapy was followed for two cycles, and the response remained durable for five months with an ongoing regimen without any immune‐related adverse events.
Atezolizumab was the first immune checkpoint inhibitor (ICI) to be introduced as a first‐line treatment option for extensive‐stage small cell lung cancer (ES‐SCLC), in combination with carboplatin and etoposide (CE) chemotherapy. However, SCLC treatment options after progression to first‐line chemotherapy are limited, warranting the readministration of previously used drugs. In combination with atezolizumab, CE readministration may theoretically be effective, based on two tentative mechanisms: its additive and synergistic effects on cytotoxic chemotherapy. The additive effect is based on the IFCT‐1603 trial in which the Kaplan‐Meier estimates of both progression‐free survival (PFS) and overall survival (OS) in the atezolizumab group exhibited a tail plateau in the selected population. Conversely, an anti‐PD‐L1 antibody synergistic effect on platinum compounds was assessed in a preclinical study, which was reinforced by clinical data. Thus, atezolizumab in combination with CE may be a treatment option in heavily treated patients. Here, we describe the first case of a heavily treated ES‐SCLC patient treated with chemoimmunotherapy, resulting in a partial response and a durable PFS.