A statistical model for the dependence between progression‐free survival and overall survival

Fleischer, Frank; Gaschler‐Markefski, Birgit; Bluhmki, Erich

doi:10.1002/sim.3637

Cited by 56 publications

(88 citation statements)

References 25 publications

(25 reference statements)

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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].…”

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 validity of surrogate endpoints has been determined by previous meta-analyses (18,19). Biostatisticians have also proposed measures for validating surrogate endpoints (20,21). Tumor response and PFS are potential surrogate endpoints for OS in extensive-stage small-cell lung cancer (22), although their validity in advanced NSCLC is controversial (23).…”

Section: Discussionmentioning

confidence: 99%

Surrogate endpoints for overall survival in advanced non-small-cell lung cancer patients with mutations of the epidermal growth factor receptor gene

Yoshino

Imai

Mori

et al. 2014

Molecular and Clinical Oncology

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Abstract. Subsequent therapies confound the ability to discern the effect of first-line chemotherapy on overall survival (OS). We investigated whether progression-free survival (PFS), post-progression survival (PPS) and tumor response were valid surrogate endpoints for OS following first-line chemotherapy in individual patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor gene mutations. We retrospectively analyzed 35 patients with advanced NSCLC treated with first-line gefitinib. The associations of PFS, PPS and tumor response with OS were analyzed. PPS was found to be strongly correlated with OS, unlike PFS and tumor shrinkage. The factors significantly associated with PPS were performance status (PS) after first-line treatment, best response to second-line treatment and number of regimens used after disease progression. PPS may be a surrogate for OS in this patient population and further therapy after disease progression following first-line chemotherapy may significantly affect OS. However, a larger study is required to validate these results.

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“…In recent years, biostatisticians have proposed various measures for validating surrogate end points [32,33]. Broglio and Berry [2 ]recently reported that the duration of PPS, which they termed survival post-progression (defined as OS minus PFS), was important for determining the applicability of OS as a measure of patient outcome.…”

Section: Discussionmentioning

confidence: 99%

Post-Progression Survival Associated with Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Docetaxel Monotherapy as Second-Line Chemotherapy

Kotake

Miura²,

Imai³

et al. 2017

Chemotherapy

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Background: In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. Methods: Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed. The relationships of PFS and PPS with OS were analyzed at the individual level. Results: Spearman rank correlation and linear regression analyses showed that PPS was strongly associated with OS (r = 0.86, p < 0.05, R² = 0.93), whereas PFS was moderately correlated with OS (r = 0.50, p < 0.05, R² = 0.21). Performance status at the end of second-line treatment and the number of regimens after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). Conclusions: In patients with advanced NSCLC with unknown oncogenic driver mutations undergoing docetaxel monotherapy as second-line chemotherapy, when compared with PFS, PPS had a stronger association with OS. This finding suggests that subsequent treatment after disease progression following second-line docetaxel monotherapy has a significant influence on OS.

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A statistical model for the dependence between progression‐free survival and overall survival

Cited by 56 publications

References 25 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

Surrogate endpoints for overall survival in advanced non-small-cell lung cancer patients with mutations of the epidermal growth factor receptor gene

Post-Progression Survival Associated with Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Docetaxel Monotherapy as Second-Line Chemotherapy

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