Response Rate Is Associated with Prolonged Survival in Patients with Advanced Non-small Cell Lung Cancer Treated with Gefitinib or Erlotinib

Tsujino, Kazuyuki; Kawaguchi, Tomoya; Kubo, Akihito; Aono, N; Nakao, Keiko; Koh, Yasuhiro; Tachibana, Kazunobu; Isa, Shun‐ichi; Takada, Minoru; Kurata, Takeshi

doi:10.1097/jto.0b013e3181a94a2f

Cited by 38 publications

(23 citation statements)

References 41 publications

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“…Our results do not correspond with some previous results that have indicated that tumor response and PFS are surrogate endpoints for OS in advanced NSCLC [24,25]. We analyzed our results pertaining to first-line therapy, and they suggested that PFS and tumor response did not adequately reflect OS in such settings.…”

Section: Discussioncontrasting

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: Discussioncontrasting

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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show abstract

“…Our results do not correspond to those of certain previous studies indicating that tumor response and PFS may be surrogate endpoints for OS in advanced NSCLC (24,25). In our patients with advanced NSCLC harboring EGFR mutations who received first-line gefitinib, PFS and tumor response did not reflect OS.…”

Section: Discussioncontrasting

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 addition, our results also showed deletions in exon 19 occurring at different amino acid positions were associated with different RR. In patients with advanced NSCLC under EGFR TKIs, the RR to EGFR TKIs correlate with the length of median PFS (29). However, at least 14% increase of RR was needed to prolong median PFS by 1 month.…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes in Non–Small Cell Lung Cancers Harboring Different Exon 19 Deletions in EGFR

Chung

et al. 2012

Clinical Cancer Research

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Purpose: Several deletions in exon 19 of epidermal growth factor receptor (EGFR) gene have been reported in non–small cell lung cancer (NSCLC). It is unknown if deletions occurring at different amino acid positions or of different sizes are associated with different clinical outcome to EGFR tyrosine kinase inhibitors (TKI). Experimental Design: This study enrolled NSCLC patients with deletions in EGFR exon 19. Patients who had received EGFR TKIs for advanced NSCLC were further evaluated for response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: In 308 patients with deletions in EGFR exon 19, 298 had deletions encompassing the entire amino acid string from L747 through E749 (LRE deletions). EGFR TKIs were used in 204 patients with advanced NSCLC. Patients with non-LRE deletions had the least RR, compared with those with deletions from E746 or L747 (42.9%, 68.2%, and 79.6%, respectively; P = 0.022). Patients with non-LRE deletions had relatively short median PFS, though not significantly different from those with deletions from E746 or L747 (5.9, 9.8, and 10.5 months, respectively; P = 0.665). The OS was not different among patients with deletions occurring at different amino acid positions (P = 0.776). Deletions in exon 19 of different sizes were not associated with different RR, PFS, or OS. Conclusions: Non-LRE deletions in exon 19 were associated with worse response to EGFR TKIs, compared with LRE deletions. Therefore, the expected clinical outcome under EGFR TKIs depends on not only the existence but also the types of deletions in exon 19. Clin Cancer Res; 18(12); 3470–7. ©2012 AACR.

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Response Rate Is Associated with Prolonged Survival in Patients with Advanced Non-small Cell Lung Cancer Treated with Gefitinib or Erlotinib

Abstract: We found a significant relationship between RR and MST in clinical trials with EGFR-TKIs. RR could be an independent surrogate marker for MST in the current response criteria in the clinical trials of EGFR-TKIs.

Cited by 38 publications

References 41 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

Clinical Outcomes in Non–Small Cell Lung Cancers Harboring Different Exon 19 Deletions in EGFR

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