Long-term partial response after camrelizumab plus chemotherapy induction therapy and camrelizumab maintenance therapy beyond two years in squamous non-small cell lung cancer: a case report

Introduction

In 2020, lung cancer was the second most diagnosed malignancy and the leading cause of cancer-related death worldwide, with 2,206,771 new cases and 1,796,144 deaths reported. Both its incidence and mortality rates have continued to increase annually (1,2). Among newly diagnosed lung cancer patients, squamous cell carcinoma accounts for approximately 29.4% of diagnoses in males and 17.1% in females (3).

Immune checkpoint inhibitors (ICIs) have become the mainstay of treatment for non-oncogene-addicted metastatic squamous non-small cell lung cancer (NSCLC) (4). Compared with chemotherapy alone, camrelizumab combined with chemotherapy has been shown to extend median overall survival (OS) to over 2 years [27.4 vs. 15.5 months; hazard ratio (HR): 0.57, 95% confidence interval (CI): 0.46–0.72; 1 − sided P<0.0001], with a 5-year survival rate approaching 30% (27.8%, 95% CI: 21.4–34.6%) (5). The KEYNOTE-024 study reported a 5-year survival rate of approximately 82.1% among patients who completed 2 years of ICI treatment (6). However, patients without a complete response (CR) after 2 years of ICI therapy have a higher risk of disease progression [odds ratio (OR): 5.06, P=0.04] (7). To date, there are no published reports on whether continued ICI treatment can further improve survival in patients who only achieve a partial response (PR) after 2 years of therapy.

In this article, we report the first case of a patient without a CR following camrelizumab plus chemotherapy and continued camrelizumab monotherapy for more than 2 years. As of July 2025, the patient had achieved a duration of response (DoR) of 49 months. This case suggests that continued ICI therapy beyond 2 years may be a key factor in prolonging survival in patients who achieve a PR after initial ICI-based treatment. We present this article in accordance with the CARE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-2095/rc).

Case presentation

In May 2021, a 62-year-old male patient was found to have multiple small pulmonary nodules on routine examination at an outside hospital. The largest nodule, measuring approximately 0.6 cm in diameter, was located subpleurally between lobes in the left-upper lobe. Scattered fibrotic streaks were observed in both lungs, without abnormal hilar structures. A soft-tissue density mass measuring approximately 4.2 cm × 3.1 cm with homogeneous density and well-defined borders was observed below the aortic arch and adjacent to the pulmonary artery. Later that same month, the patient presented to the Department of Medical Oncology at The Second Affiliated Hospital of Dalian Medical University for further evaluation and treatment. The patient had been in good general health, with the only notable diagnosis being a callus on the third toe of the left foot in June 2021. He had a 37-year history of smoking approximately 20 cigarettes per day and had not yet quit smoking. There was no family history of malignancy or known hereditary disorders.

Contrast-enhanced chest computed tomography (CT) revealed a soft-tissue mass near the left-upper hilar region, measuring approximately 44 mm × 28 mm, with moderate and heterogeneous enhancement on contrast scan. The lesion was considered highly suspicious for lung cancer. Multiple small nodules were also noted in both lungs. No evidence of metastasis was found on brain magnetic resonance imaging, abdominal CT, or bone scintigraphy (emission CT).

At the end of May 2021, the patient underwent CT-guided percutaneous needle biopsy of the lesion in the left-upper lobe. Histopathological examination revealed NSCLC, favoring poorly differentiated squamous cell carcinoma. His immunohistochemistry results were as follows: P40 (+), CK5/6 (+), TTF-1 (−), CD56 (−), Syn (−), CgA (−), Napsin A (−), and Ki-67 (index 50%). The final diagnosis of the patient was cT2bN0Mx squamous NSCLC.

To achieve better therapeutic outcomes, beginning in June 2021, the patient elected to receive camrelizumab [200 mg, intravenous (IV) infusion, day 1, every 21 days] in combination with paclitaxel (300 mg, IV infusion, day 1) and carboplatin (400 mg, IV infusion, day 1, every 21 days). After two treatment cycles, radiological assessment showed a PR, with significant shrinkage of the mass adjacent to the left-upper hilar region, and a reduction in the size of some bilateral pulmonary nodules. These intrapulmonary nodules were considered metastatic, and the disease was staged as stage IV, with no surgical indication; therefore, the patient continued the same regimen. A total of six cycles of chemotherapy combined with camrelizumab were completed, with the final cycle administered in December 2021. Before the fourth cycle, the patient developed reactive capillary hemangiomas, a known immune-related adverse event of camrelizumab, resulting in bleeding from ruptured superficial capillaries on the scalp. Camrelizumab was withheld for one cycle, and thalidomide was initiated, leading to marked improvement in the hemangiomas. Beginning in October 2021, due to restrictions related to the coronavirus disease 2019 pandemic, the patient could only receive camrelizumab maintenance therapy once every 1–2 months, which was continued until April 2024.

A follow-up contrast-enhanced chest CT performed on November 8, 2024 showed a soft-tissue shadow along the left-upper hilar-mediastinal border, scattered small nodules in both lungs (recommended for continued follow up), fibrotic lesions in the middle lobe of the right lung, dependent changes in the lower lobes of both lungs, and an intratracheal nodule suspected to be a mucus plug. In December 2024, follow-up chest CT showed a soft-tissue shadow along the left-upper hilar-mediastinal border, which was generally unchanged compared to the previous scan on April 8, 2024. Scattered small nodules in both lungs were also similar to prior findings. As of July 2025, telephone follow up confirmed the patient was alive. The patient’s treatment course, tumor marker dynamics, and imaging assessments are summarized in Figure 1. All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was provided by the patient. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 Timeline of laboratory findings, treatments, and imaging. CYFRA21-1, cytokeratin 19 fragment 21-1; NSE, neuron-specific enolase; SCC, squamous cell carcinoma; ULN, upper limit of normal.

International multidisciplinary team (iMDT) discussion

Discussion of physicians from the Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University

To our knowledge, this is the first reported case of long-term survival in a patient with squamous NSCLC who achieved a PR following first-line treatment with ICI plus chemotherapy and continued ICI therapy for more than 2 years.

In the CameL-sq study, an independent review committee compared the objective response rates (ORRs), median progression-free survival (PFS), and median DoR of a camrelizumab plus chemotherapy group and a chemotherapy-alone group, which were 64.8% vs. 36.7%, 8.5 (95% CI: 6.9–10.4) vs. 4.9 (95% CI: 4.2–5.5) months, and 13.1 (95% CI: 9.3–15.7) vs. 4.4 (95% CI: 4.2–4.9) months, respectively (8). These results suggest that the addition of camrelizumab to chemotherapy enhances treatment sensitivity and prolongs the DoR in patients with squamous NSCLC. However, patients with a DoR exceeding 2 years remain rare.

Among the ICIs currently approved for the first-line treatment of squamous NSCLC, pembrolizumab, nivolumab plus ipilimumab, camrelizumab, sugemalimab, cemiplimab, and serplulimab have an upper limit of 2 years for treatment duration, whereas atezolizumab, durvalumab (with or without tremelimumab), and tislelizumab do not have any such limitations (8-16). Nevertheless, a meta-analysis found no statistically significant differences in the PFS or OS HRs between different ICIs (17). Two observational studies have suggested that for patients with NSCLC who have received more than 2 years of ICI therapy, continued treatment does not confer any additional survival benefit compared to stopping therapy (18,19). Due to the absence of randomized controlled trial (RCT) evidence, the optimal approach for patients who complete two years of ICI therapy remains uncertain.

A biomarker analysis from the CameL-sq study revealed that circulating tumor DNA (ctDNA) clearance after two treatment cycles was independently associated with significantly longer PFS (P<0.0001) in the camrelizumab plus chemotherapy group. Additionally, the risk of disease progression in this group was lower than that in the chemotherapy-alone group across all levels of programmed cell death ligand 1 (PD-L1) expression (8). A retrospective Australian cohort study indicated that among NSCLC patients who completed 2 years of pembrolizumab therapy, those with a PD-L1 tumor proportion score (TPS) <1% and without a CR were more likely to experience disease progression (7). Clinical trials are currently ongoing to determine the optimal duration of ICI therapy guided by liquid biopsy, but no definitive conclusions are available as yet (20). Therefore, in the absence of clear evidence showing no survival benefit from continued ICI therapy beyond 2 years in NSCLC patients, it may be reasonable to consider extended treatment for those with a PD-L1 TPS <1% and/or without a CR. Further, patients should be involved in shared decision making, as the psychological acceptance of long-term treatment and financial burden are important factors influencing adherence.

This case report had two limitations. A primary limitation of this study is the absence of a control group and the limited sample size, which preclude definitive attribution of the observed long-term PR to extended camrelizumab therapy, as potential confounding factors such as individual patient biology or lifestyle influences cannot be ruled out. Second, due to financial constraints, the patient did not undergo testing for driver gene mutations, PD-L1 expression, or ctDNA, limiting our ability to explore the potential biomarkers associated with a long-term survival benefit.

Several issues regarding the treatment of this patient were further discussed as follows

Question 1: the patient is currently maintaining PR. Current clinical evidence generally recommends a maximum duration of immunotherapy maintenance of no more than 2 years. For patients who achieve a rapid response and maintain stable disease, should a shorter duration of maintenance therapy be considered?

Nobuaki Kobayashi: At present, most pivotal clinical trials (e.g., KEYNOTE-024, CheckMate 153, CameL-sq) have set a maximum duration of 2 years for immunotherapy, primarily for pragmatic and safety considerations.

However, this does not represent a definitive scientific threshold. There is no robust randomized evidence to support shortening the duration to less than two years in patients who achieve a PR and remain clinically stable. Retrospective studies suggest that stopping after two years may yield similar survival compared to continuation, but data for shorter treatment are lacking.

In real-world clinical practice, many physicians continue immunotherapy even beyond 2 years, including in patients who achieve a CR, reflecting uncertainties regarding the optimal duration and concerns about disease relapse.

Therefore, discontinuation cannot be recommended at this stage, and treatment duration should be individualized based on efficacy, tolerability, patient preference, and economic burden.

Toshiyuki Sumi: In the absence of randomized data, many pivotal trials capped ICI at ~2 years, and this remains a reasonable default. For patients with a rapid response and durable PR without toxicity, an individualized approach is appropriate: consider stopping at 1–2 years with shared decision-making and close surveillance, especially if cumulative immune-related adverse events, cost, or patient preference favor discontinuation. Re-challenge at progression is a pragmatic option in selected cases.

Question 2: are there currently precise methods available to monitor the emergence of immune resistance in patients who initially respond to immunotherapy?

Nobuaki Kobayashi: Currently, there are no fully validated clinical tools to precisely monitor the onset of immune resistance. Several approaches are under investigation:

ctDNA: clearance or re-emergence during treatment has shown promise as an early marker of resistance.

Peripheral immune profiling: dynamic changes in circulating T-cell subsets (e.g., CD8⁺ T cells, regulatory T cells) or cytokine signatures may reflect evolving resistance.

Repeat tumor biopsy: loss of antigen presentation (e.g., MHC-I or β2-microglobulin loss) can confirm resistance mechanisms.

While these are promising, they remain largely exploratory and are not yet standardized for routine clinical practice.

Toshiyuki Sumi: There is no single precise, validated clinical test to detect resistance pre-emptively. In practice, we rely on serial imaging and clinical assessment. The ctDNA kinetics can sometimes anticipate radiographic progression and may be useful where available, but it is not yet standardized. Exploratory signals (e.g., evolving mutational profiles, antigen-presentation defects) are of research interest but not routinely actionable in daily practice.

Question 3: immune resistance to immunotherapy involves multiple intra- and extra-tumoral mechanisms, including defects in antigen presentation and oncogenic signaling pathway-mediated immunosuppression. What strategies are currently recommended to overcome such immune resistance, and are there any biomarkers available to predict prognosis?

Nobuaki Kobayashi: Immune resistance is multifactorial, involving tumor-intrinsic and extrinsic mechanisms. Several strategies are currently being explored to overcome resistance:

Combination therapies: ICIs with chemotherapy, anti-vascular endothelial growth factor (VEGF) agents, or radiotherapy to remodel the tumor microenvironment.

Dual checkpoint inhibition: e.g., programmed cell death protein 1 (PD-1)/PD-L1 inhibitors combined with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or lymphocyte-activation gene 3 (LAG-3) blockade.

Novel immunomodulators: stimulator of interferon genes (STING) agonists, Toll-like receptor (TLR) agonists, or oncolytic viruses to enhance antigen presentation and T-cell priming.

Prognostic biomarkers under investigation include: PD-L1 expression (limited predictive accuracy), tumor mutational burden (TMB), dynamic ctDNA changes, genomic alterations such as STK11, KEAP1, or B2M loss, which may be associated with poor response or acquired resistance.

Currently, no single biomarker is sufficient, and integrative approaches combining tissue, blood-based, and immune profiling are likely needed for future precision medicine.

Toshiyuki Sumi: For acquired/oligoprogressive resistance, local ablative therapy (SBRT/surgery) while continuing ICI can prolong benefit. For systemic progression, consider chemotherapy-ICI combinations or adding anti-angiogenic therapy where appropriate; clinical-trial enrollment (e.g., combinations targeting TIGIT, LAG-3, or other pathways) is encouraged. Biomarkers with some prognostic/predictive value include PD-L1 expression, TMB, and genomic co-alterations (e.g., STK11/KEAP1), as well as interferon-γ-related signatures and features of antigen presentation; however, their utility remains context-dependent and imperfect at the individual level. Microbiome-based markers are promising but remain investigational.

Conclusions

For patients with squamous NSCLC who achieve a PR and maintain disease control for more than 2 years following first-line treatment with ICIs plus chemotherapy, continued immunotherapy should be considered until disease progression or loss of clinical benefit. Large-scale RCTs are needed to provide definitive evidence to guide clinical decision making.

Acknowledgments

We would like to thank Yang Wang (a medical writer at Suzhou Suncadia Biopharmaceuticals Co., Ltd.) for technical editing.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-2095/rc

Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-2095/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-2095/coif). T.S. reports receiving honoraria for lectures, presentations, or educational events from AstraZeneca, Ono Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was provided by the patient. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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