Camrelizumab for Advanced Squamous Non-Small Cell Lung Carcinoma: Caicun Zhou, MD, PhD

Caicun Zhou, MD, PhD.

Recently, the results of a phase 3 trial on camrelizumab were published in the Journal of Thoracic Oncology and presented at the European Lung Cancer Virtual Congress 2021. Camrelizumab was studied in the randomized, double-blind, multicenter trial as a treatment for advanced squamous non-small cell lung carcinoma (NSCLC). Patients with stages IIIB-IV squamous NSCLC were treated with carboplatin plus paclitaxel with camrelizumab or placebo in the first-line setting. Compared with those who received placebo, patients who were treated with camrelizumab had a significantly prolonged progression-free survival and overall survival. In this interview, principal investigator Caicun Zhou, MD, PhD, of the Shanghai Pulmonary Hospital, who presented the results at the European Lung Cancer Virtual Congress, speaks with Oncology Data Advisor about NSCLC and camrelizumab’s place in the treatment of this disease.

Can you explain some of the differences in treating squamous and non-squamous NSCLC?

Caicun Zhou, MD, PhD: The major differences in treating squamous and non-squamous NSCLC lie in two aspects. First, we have had major advances beyond the standard cytotoxic options, owing to the development of targeted therapies and the addition of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), and other anti-cancer agents targeting driver genes including ROS1 (c-ros oncogene 1) and RET (rearranged during transfection) to the treatment arsenal for NSCLC. However, these advances in targeted therapy mostly apply to patients with non-squamous disease—predominantly lung adenocarcinoma, while patients with squamous carcinoma remain stuck in the era of chemotherapy before the advent of immunotherapy. In addition, maintenance therapy is an important treatment strategy in the management of advanced or metastatic NSCLC. Both bevacizumab and pemetrexed are effective as maintenance therapy for non-squamous NSCLC; however, there is no approved maintenance therapy for squamous NSCLC.

How does camrelizumab compare with other established and emerging therapies for squamous NSCLC?

Dr. Zhou: To our knowledge, CameL-sq (NCT03668496) is the first study to report a progression-free survival greater than three months with the addition of an immune checkpoint inhibitor (ICI) to chemotherapy for treatment of squamous NSCLC in the overall population of a phase 3 trial. While the final overall survival data are still pending, a 45% reduction in risk of death was observed with camrelizumab plus chemotherapy by data cutoff despite a high crossover rate. In addition, survival benefits observed with camrelizumab plus chemotherapy were generally consistent across predefined subgroups.

Two earlier global trials have assessed an ICI in combination with platinum-based chemotherapy in untreated patients with metastatic squamous NSCLC. In KEYNOTE-407 (NCT02775435), pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel significantly improved both median progression-free survival and overall survival versus placebo plus chemotherapy alone. In IMpower131 (NCT02367794), the addition of atezolizumab to carboplatin and nab-paclitaxel improved median progression-free survival but not overall survival in the overall population. Additionally, two phase 3 trials—RATIONALE 307 (NCT03594747) and ORIENT-12 (NCT03629925)—evaluated an ICI plus standard chemotherapy specifically in Chinese patients with advanced squamous NSCLC. Significant progression-free survival improvement was reported with immune combination therapy for both trials, while overall survival data was not mature. In CameL-sq, the median progression-free survival of 4.9 months observed for the chemotherapy control arm was comparable to the 4.9–5.6 months reported in previous studies of squamous NSCLC; however, the progression-free survival for the combination immunotherapy arm was superior to previous reports in the same setting, with a progression-free survival gain of 3.6 months and a 63% reduced risk of progression or death as compared with a progression-free survival gain of 0.6–2.9 months and a 29%–52% reduced risk of progression or death. The progression-free survival benefits for camrelizumab plus chemotherapy were driven by a high overall response rate, as well as remarkable response durability; the overall response rate of 64.8% and median duration of response of 13.1 months with camrelizumab plus chemotherapy compared favorably with the overall response rate of 44.7%–74.8% and median duration of response of 7.3–8.6 months reported for other ICI and chemotherapy combinations as first-line treatment for squamous NSCLC. By data cutoff, a 45% reduction in risk of death was also seen with camrelizumab plus chemotherapy versus placebo plus chemotherapy, despite the crossover of 46.9% of patients from the placebo plus chemotherapy group after disease progression. The safety profile of camrelizumab plus carboplatin-based chemotherapy was generally consistent with the known toxicity profiles of the individual components and with those observed for camrelizumab plus chemotherapy in non-squamous NSCLC. Our findings from CameL-sq support camrelizumab plus chemotherapy as a first-line treatment for advanced NSCLC without sensitizing EGFR/ALK alterations, regardless of histology or programmed death-ligand 1 (PD-L1) expression status.

How do you see the treatment of squamous NSCLC changing in light of your results?

Dr. Zhou: Although immuno-oncology plus chemotherapy is the standard of care, as we can see from the results of CameL-sq, as well as KEYNOTE-407, IMpower131, RATIONALE 307, and ORIENT-12, the efficacy and safety profiles vary from compound to compound. The reasons for these differences remain to be explored.

What advice do you have for clinicians who are managing patients with squamous NSCLC?

Dr. Zhou: Immuno-oncology plus chemotherapy is currently the standard of care for treatment of squamous NSCLC. I would recommend that clinicians select immuno-oncology therapies based on efficacy data, safety profile, and accessibility in clinical practice.

About Dr. Zhou

Caicun Zhou, MD, PhD, is the Director of the Department of Oncology at Shanghai Pulmonary Hospital, Director of the Cancer Institute of Tongji University Medical School, and Chairman of the Oncology Department of Tongji University in China. Dr. Zhou’s research interests include customized and targeted lung cancer therapy, and he has authored numerous publications. Dr. Zhou is a member of the Chinese Association of Lung Cancer, the Chinese Society of Clinical Oncology, the Shanghai Anti-Cancer Association, the Shanghai Pneumonology Association, and the Shanghai Oncology Association.

For More Information

Zhou C, Ren S, Chen J, et al (2021). Camrelizumab or placebo plus carboplatin and paclitaxel as first-line treatment for advanced squamous NSCLC (CameL-sq): a randomized, double-blind, multicenter, phase III trial. J Thorac Oncol (European Lung Cancer Virtual Congress 2021), 16(suppl_4). Abstract 960. DOI:10.1016/S1556-0864(21)01938-9 (2021). A study of SHR-1210 in combination with carboplatin + paclitaxel in subjects with squamous NSCLC. NLM identifier: NCT03668496. (2020). A study of carboplatin-paclitaxel/nab-paclitaxel chemotherapy with or without pembrolizumab (MK-3475) in adults with first line metastatic squamous non-small cell lung cancer (MK3475-407/KEYNOTE-407). NLM identifier: NCT02775435. (2021). A study of atezolizumab in combination with carboplatin + paclitaxel or carboplatin + nab-paclitaxel compared with carboplatin + nab-paclitaxel in participants with stage IV squamous non-small cell lung cancer (NSCLC) [IMpowerr131]. NLM identifier: NCT02367794. (2020). A study tislelizumab in combination with chemotherapy versus chemotherapy in advanced lung cancer. NLM identifier: NCT03594747. (2021). Sintilimab in combination with gemcitabine and platinum-based chemotherapy as first-line therapy for advanced or metastatic squamous NSCLC. NLM identifier: NCT03629925.

Transcript edited for clarity. Any views expressed above the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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