Surrogate markers predicting overall survival for lung cancer: ELCWP recommendations

Berghmans, T.; Pasleau, Françoise; Paesmans, Marianne; Bonduelle, Y.; Cadranel, J.; Toth, I. Cs; Garcia, C.; Giner, Vicente; Holbrechts, Stéphane; Lafitte, Jean-Jacques; Lecomte, Jacques; Louviaux, I.; Markiewicz, Eveline; Meert, Anne-Pascale; Richez, Michel; Roelandts, Martine; Scherpereel, Arnaud; Tulippe, Ch.; Houtte, Paul Van; Schil, Paul Van; Wachters, C.; Westeel, Virginie; Sculier, J.P.

doi:10.1183/09031936.00190310

Cited by 35 publications

(25 citation statements)

References 148 publications

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“…In recent years, biostatisticians have proposed a wide variety of measures for validating surrogate endpoints [20,21]. Although tumor response and PFS are potential surrogate endpoints for OS in extensive-stage small cell lung cancer [22], their validity is controversial in advanced NSCLC [23]. Broglio et al recently focused on PPS, which they termed as survival post progression (defined as OS minus PFS), in a hypothetical clinical trial setting under the assumption that treatment affected PFS but not PPS [2].…”

Section: Discussionmentioning

confidence: 99%

Individual-level data on the relationships of progression-free survival, post-progression survival, and tumor response with overall survival in patients with advanced non-squamous non-small cell lung cancer

Imai¹,

Takahashi²,

Mori³

et al. 2014

neo

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The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), or tumor response could be valid surrogate endpoints for OS after first-line chemotherapies in advanced NSCLC by using individual-level data, given the lack of research in this area. Between April 2009 and June 2011, 50 patients with advanced non-squamous NSCLC treated with cisplatin and pemetrexed as first-line chemotherapy were analyzed. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.89, P < 0.05, R 2 = 0.79), PFS was moderately correlated with OS (r = 0.67, P < 0.05, R 2 = 0.39), and tumor shrinkage was weakly correlated with OS (r = 0.36, P < 0.05, R 2 = 0.14). Performance status at the beginning of second-line treatment, the best response to second-line treatment, and number of regimens used after progression following first-line chemotherapy were significantly associated with PPS (P < 0.05). Analysis of individual-level data suggested that PPS could be used as a surrogate for OS in patients with advanced nonsquamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS. These results should be validated in other larger populations. Key words: non-small cell lung cancer, overall survival, post-progression survival, progression-free survival, tumor responseLung cancer is the most common cause of cancerrelated mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of lung cancers [1]. Overall survival (OS) is considered the most reliable endpoint in cancer studies, and when studies can be conducted to adequately assess survival, it is usually the preferred endpoint [2]. This endpoint is precise, easy to measure, and can be documented by the date of death. Surrogate endpoints such as tumor response and progression-free survival (PFS) are also useful endpoints for phase II oncology clinical trials because they can be measured earlier, can be measured more conveniently, and occur more frequently than the main endpoints of interest, which are referred to as the true endpoints.In view of the growing number of drugs and combinations thereof that are available for the treatment of NSCLC, the effects of first-line chemotherapy on OS might be confounded by subsequent therapies [3]. Indeed, PFS improvements do not necessarily result in an improved OS, as shown by recent randomized trials in patients with NSCLC [4]. In recent years, as for breast, ovarian, and colorectal cancers [5][6][7], a growing number of active compounds are available for second-or third-line chemotherapy for advanc...

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Section: Discussionmentioning

confidence: 99%

Individual-level data on the relationships of progression-free survival, post-progression survival, and tumor response with overall survival in patients with advanced non-squamous non-small cell lung cancer

Imai¹,

Takahashi²,

Mori³

et al. 2014

neo

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“…The significance of CTCs has not been well established for lung cancer; however, several studies have reported that the detection of CTCs may be a prognostic factor for lung cancer subsequent to surgical and chemotherapeutic treatment (17)(18)(19). Since NSCLC lacks validated biomarkers, a radiological response is recognized as a surrogate for survival or recurrence (20). CTC count may be an additional prognostic factor for survival, recurrence and response to treatment.…”

Section: Discussionmentioning

confidence: 99%

Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

et al. 2017

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Abstract. The detection of circulating tumor cells (CTCs) is limited by the rarity of these cells in the peripheral blood of patients with cancer. Understanding tumor biology may be useful in the development of novel therapeutic strategies for patients with lung cancer. The present study evaluated a novel size-based filtration platform for enriching CTCs from patients with lung cancer. Blood samples were obtained from 82 patients with lung cancer for CTC analysis. CTC enrichment by size-based filtration was performed on 5-ml blood samples. The collected cells were detected by immunofluorescence using monoclonal anti-human antibodies against protein tyrosine phosphatase, receptor type C (CD45) and epithelial cell adhesion molecule (EpCAM; an epithelial cell marker), as well as a DAPI nucleic acid stain. CTCs were detected in 57 patients (69.5%) using the size-based filtration platform. The mean CTC counts, defined as the number of cells with DAPI-positive, CD45-negative and EpCAM-positive staining, were 1.48±1.71 per 5 ml blood for the 66 stage I-III patients and 8.00±9.95 per 5 ml blood for the 16 stage IV patients. The presence of ≥1 CTCs per 5-ml blood sample was significantly associated with pathological stage (stage IV vs. stage I-III, P=0.009), but not with patient age or gender, tumor histology, tumor size or lymphovascular invasion. The mean CTC count of healthy donors was 0.25±0.55 per 5 ml blood. In summary, CTCs from the blood of patients with lung cancer were enriched using a size-based filtration platform and immunofluorescent staining with DAPI, CD45 and EpCAM. The CTC counts of patients with stage IV cancer were higher than those of patients with stages I-III cancer. These results suggest that this novel platform may be a useful tool for determining the prognosis of patients with lung cancer.

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“…One issue is the lack of surrogate markers of antitumor activity that could provide an early indication of response to therapy and help guide clinical decision making (11). A second issue is the inherent difficulty in obtaining representative lung tumor specimens to explore and validate predictive tissue biomarkers of targeted therapies (12).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Circulating Tumor Cells and Circulating Tumor DNA in Non–Small Cell Lung Cancer: Association with Clinical Endpoints in a Phase II Clinical Trial of Pertuzumab and Erlotinib

Punnoose

Atwal

Liu

et al. 2012

Clinical Cancer Research

379

295

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Purpose: Elevated levels or increases in circulating tumor cells (CTC) portend poor prognosis in patients with epithelial cancers. Less is known about CTCs as surrogate endpoints or their use for predictive biomarker evaluation. This study investigated the utility of CTC enumeration and characterization using the CellSearch platform, as well as mutation detection in circulating tumor DNA (ctDNA), in patients with advanced non-small cell lung cancer (NSCLC).Experimental Design: Forty-one patients were enrolled in a single-arm phase II clinical trial of erlotinib and pertuzumab. Peripheral blood was analyzed for CTC enumeration, EGFR expression in CTCs, and detection of oncogenic mutations in CTCs and ctDNA. Changes in CTC levels were correlated with 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomographic (FDG-PET) and computed tomographic (CT) imaging and survival endpoints.Results: CTCs were detected (1 CTC) at baseline in 78% of patients. Greater sensitivity for mutation detection was observed in ctDNA than in CTCs and detected mutations were strongly concordant with mutation status in matched tumor. Higher baseline CTC counts were associated with response to treatment by Response Evaluation Criteria in Solid Tumors (RECIST, P ¼ 0.009) and decreased CTC counts upon treatment were associated with FDG-PET and RECIST response (P ¼ 0.014 and P ¼ 0.019) and longer progression-free survival (P ¼ 0.050).Conclusion: These data provide evidence of a correlation between decreases in CTC counts and radiographic response by either FDG-PET or RECIST in patients with advanced NSCLC. These findings require prospective validation but suggest a potential role for using CTC decreases as an early indication of response to therapy and ctDNA for real-time assessment of mutation status from blood.

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Surrogate markers predicting overall survival for lung cancer: ELCWP recommendations

Cited by 35 publications

References 148 publications

Individual-level data on the relationships of progression-free survival, post-progression survival, and tumor response with overall survival in patients with advanced non-squamous non-small cell lung cancer

Individual-level data on the relationships of progression-free survival, post-progression survival, and tumor response with overall survival in patients with advanced non-squamous non-small cell lung cancer

Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

Evaluation of Circulating Tumor Cells and Circulating Tumor DNA in Non–Small Cell Lung Cancer: Association with Clinical Endpoints in a Phase II Clinical Trial of Pertuzumab and Erlotinib

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