Camrelizumab Plus Carboplatin, Nab-Paclitaxel Shows Efficacy in ES-SCLC

The anti-PD-1 monoclonal antibody camrelizumab may be a viable first-line treatment option for patients with extensive-stage small cell lung cancer (ES-SCLC) in combination with carboplatin and nab-paclitaxel (Abraxane; Bristol Myers Squibb), according to a new study.

The authors of the new phase 2 study also identified biomarkers that were associated with patient outcomes. The report was published in the journal MedComm.¹

Approximately three-quarters of patients with SCLC are not diagnosed until their disease has reached extensive stage status,² the authors noted. Those patients are typically given platinum-based chemotherapy. The use of irinotecan (Camptosar; Pfizer) has been limited in clinical practice due to its toxicity and “relatively poor absolute survival benefit,” they noted.³

“Therefore, first-line chemotherapeutic drugs available for patients with ES-SCLC are relatively limited,” the authors wrote.¹

PD-1 blockade has previously shown success in a first-line setting in ES-SCLC, and nab-paclitaxel is albumin-bound and solvent-free, which the investigators explained may minimize the toxicity associated with paclitaxel therapy. | Image credit: didesign - stock.adobe.com

There are several reasons why the combination of camrelizumab plus carboplatin and nab-paclitaxel could help fill that gap, the investigators noted. PD-1 blockade has previously shown success in a first-line setting in ES-SCLC, and nab-paclitaxel is albumin-bound and solvent-free, which the investigators explained may minimize the toxicity associated with paclitaxel therapy.

To better understand how the combination therapy might work in a first-line setting, the investigators recruited 60 patients with ES-SCLC between March 2021 and December 2022. The participants had a median age of 65, though they ranged in age from 38 to 74 years. All but 10 of the participants were male; most (n = 40) were former smokers. All of the participants had an Eastern Cooperative Oncology Group performance status of 1, and most (n = 52) had stage IV disease at diagnosis.

Participants were given camrelizumab plus carboplatin and nab-paclitaxel every 3 weeks for 4 to 6 cycles. After that, maintenance camrelizumab was delivered until progression or until toxicity was intolerable.

The median follow-up duration was 19.3 months (95% CI, 16.2-22.8 months). At that point, 10 patients (16.7%) were still receiving treatment. The other 10 discontinued the treatment. Reasons for discontinuation included disease progression (n = 36; 60%), patient decision (n = 7; 11.7%), adverse events (n = 6; 10%), or the end of therapy per study design (n = 1; 1.7%).

In terms of efficacy, the 6-month progression-free survival (PFS) rate was 52.2% (95% CI, 39.8%-68.5%). The median PFS was 7.1 months (95% CI, 5.5-9.7 months). The median overall survival (OS) was 18.1 months (95% CI, 12.9-not reached). The 1-year OS rate was 68.4% (95% CI, 56.8%-82.3%). The overall response rate was 73.3%, and the disease control rate was 93.3%.

As of the study’s cutoff, 27 participants had died. Overall, 36 participants either experienced disease progression or death. Adverse events were in line with expectations. Of the original 60 participants, the high-quality baseline tumor samples were available for 38 participants. Those samples were then used in a biomarker analysis.

The biomarker analysis suggested that MUC17 alterations or high NEUROG1 depression were associated with a significantly shorter PFS and OS. The authors also applied de novo non-negative matrix factorization to raw RNA sequencing data, which revealed 2 well-defined subsets of patients with different immune features that were aligned with clinical outcomes with first-line chemo-immunotherapy.

“These findings together suggest that deeper understanding of [the] tumor immune microenvironment by integrating multiomic data would be helpful to uncover the complex mechanisms underlying chemo-immunotherapy response,” they wrote.

Overall, the investigators concluded their study shows camrelizumab plus carboplatin and nab-paclitaxel holds potential as an alternative first-line therapy in ES-SCLC.

References

1. Yu J, Cai D, Zhao S, et al. Camrelizumab, an anti-PD-1 monoclonal antibody, plus carboplatin and nab-paclitaxel as a first-line setting for extensive-stage small-cell lung cancer: a phase 2 trial and biomarker analysis. MedComm (2020). 2025;6(8):e70300. doi:10.1002/mco2.70300

2. Schwendenwein A, Megyesfalvi Z, Barany N, et al. Molecular profiles of small cell lung cancer subtypes: therapeutic implications. Mol Ther Oncolytics. 2021;20:470-483. doi:10.1016/j.omto.2021.02.004

3. Hanna N, Bunn PA Jr, Langer C, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006;24(13):2038-2043. doi:10.1200/JCO.2005.04.8595