The Value of Early Depth of Response in Predicting Long-Term Outcome in EGFR-Mutant Lung Cancer

Lee, Chee Khoon; Lord, Sarah J.; Marschner, Ian C.; Wu, Yi‐Long; Sequist, Lecia V.; Rosell, Rafael; Fukuoka, Masahiro; Mitsudomi, Tetsuya; Asher, Rebecca; Davies, Lucy; Gebski, Val; Gralla, Richard J.; Mok, Tony; Yang, James Chih‐Hsin

doi:10.1016/j.jtho.2018.03.010

Cited by 18 publications

(31 citation statements)

References 36 publications

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“…We further analyzed the depth of response to first‐line EGFR‐TKIs and median PFS and found no significant association. Our results reiterate those of two recent studies . In a study by Wu et al, although patients who achieved a partial response had significantly longer PFS and overall survival at 16.5 and 56 weeks, respectively, higher tumor shrinkage was not related to better PFS or overall survival .…”

Section: Discussionsupporting

confidence: 89%

Larger tumors are associated with inferior progression‐free survival of first‐line EGFR‐tyrosine kinase inhibitors and a lower abundance of EGFR mutation in patients with advanced non‐small cell lung cancer

et al. 2019

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Background The impact of primary tumor size on the therapeutic outcomes of EGFR‐tyrosine kinase inhibitors (TKIs) in advanced non‐small cell lung cancer (NSCLC) with EGFR mutation remains unclear. Methods A total of 291 consecutive patients with advanced EGFR ‐mutant NSCLC administered first‐line EGFR‐TKIs were enrolled. Computed tomography was used to assess primary tumor diameter. The amplification refractory mutation system plus was used to quantitatively evaluate the abundance of EGFR mutations. Associations between depth of response, abundance of EGFR mutations, and tumor size was investigated. Results Patients were divided into three groups according to T classification: ≤ 3 cm ( n = 109), 3–5 cm ( n = 121), and > 5 cm ( n = 61). Median progression‐free survival (PFS) was significantly longer in the ≤ 3 cm and 3–5 cm groups compared to the > 5 cm group (10.8 vs. 10.5 vs. 7.1 months; P < 0.001). Subgroup analysis revealed a consistent result in patients with exon 19 deletion and 21 L858R mutation. Multivariate analysis revealed that tumor size was an independent predictive factor for PFS (hazard ratio 1.528, 95% confidence interval 1.104–2.115; P = 0.010). Larger tumors (> 5 cm) were marginally significantly less EGFR ‐mutant abundant than smaller tumors (≤ 5 cm) (mean ± standard deviation 30.5 ± 29.5% vs. 45.8 ± 43.1%; P = 0.08). Conclusion Larger tumors (> 5 cm) were associated with inferior PFS of first‐line EGFR‐TKI therapy in advanced NSCLC patients with activating EGFR mutations. A potential explaination might be that EGFR mutations are less abundant in larger tumors.

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Section: Discussionsupporting

confidence: 89%

Larger tumors are associated with inferior progression‐free survival of first‐line EGFR‐tyrosine kinase inhibitors and a lower abundance of EGFR mutation in patients with advanced non‐small cell lung cancer

et al. 2019

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“…Our first result is that there is no correlation between volume-based imaging biomarkers and survival. This finding is consistent with the work [12] who noticed a lack of association between tumor shrinkage and long-term survival. This illustrates why the response to TKI treatment is difficult to estimate using only the evolution of tumor volume (or RECIST).…”

Section: Discussionsupporting

confidence: 93%

“…Concerning EGFR-mutated non-small cells lung carcinoma, previous works have studied the correlations between the initial reduction of the primary tumor and the overall survival. One can find contradictory results in the literature: in [10, 11], a significant correlation has been established but more recently in [12] this correlation has not be validated using another database. Many recent studies propose to use radiomic approaches which consist in extracting a large number of quantitative features from medical images using data-characterization algorithms.…”

Section: Introductionmentioning

confidence: 99%

A novel imaging biomarker for survival prediction in EGFR-mutated NSCLC patients treated with TKI

Collin

Groza

Missenard

et al. 2019

Preprint

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“…Nevertheless, DpR was not associated with PFS or OS in 2 studies involving patients with epidermal growth factor receptor ( EGFR ) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) . Furthermore, in a pooled analysis involving patients with EGFR mutations enrolled in 5 randomized clinical trials comparing EGFR TKIs with chemotherapy, no association was found between DpR at 6 or 12 weeks and long‐term survival among patients treated with either an EGFR TKI or chemotherapy . There are several reasons for the discordant results between the chemotherapy arms from the pooled analysis and our study.…”

Section: Discussioncontrasting

confidence: 51%

“…11,12 Furthermore, in a pooled analysis involving patients with EGFR mutations enrolled in 5 randomized Cancer July 15, 2019 clinical trials comparing EGFR TKIs with chemotherapy, no association was found between DpR at 6 or 12 weeks and long-term survival among patients treated with either an EGFR TKI or chemotherapy. 13 There are several reasons for the discordant results between the chemotherapy arms from the pooled analysis and our study. Perhaps the main differences are in methodology.…”

Section: Discussionmentioning

confidence: 56%

Association between depth of response and survival in patients with advanced‐stage non–small cell lung cancer treated with first‐line chemotherapy

Morgensztern

Ko²,

O’Brien

et al. 2019

Cancer

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Background A partial response according to the Response Evaluation Criteria in Solid Tumors includes a wide range of changes in tumor size. This study evaluated whether further specification of tumor reduction based on the depth of response (DpR) would provide a more precise association with outcomes for patients with non–small cell lung cancer (NSCLC) treated with first‐line platinum‐based chemotherapy. Methods A retrospective analysis was performed for the randomized phase 3 CA031 trial in patients with NSCLC treated with carboplatin in combination with nab‐paclitaxel or solvent‐based paclitaxel. Quartiles according to the maximum tumor reduction from the baseline were defined (quartile 1 [Q1], >0% to 25%; quartile 2 [Q2], >25% to 50%; quartile 3 [Q3], >50% to 75%; and quartile 4 [Q4], >75%) and were compared with those patients with no tumor reduction (NTR). The primary objective was to evaluate the association between DpR and overall survival (OS). Results Of the 1052 patients enrolled in the CA031 trial, 959 (91%) were evaluable, and they included 365 (38.1%) who were classified as Q1, 327 (34.1%) who were classified as Q2, 131 (13.7%) who were classified as Q3, and 34 (3.5%) who were classified as Q4; 102 had NTR (10.6%). The median OS values for patients in the NTR, Q1, Q2, Q3, and Q4 groups were 4.8, 10.4, 14.5, 19.3, and 23.5 months, respectively. The maximum DpR on treatment was an independent predictor of improved OS in comparison with patients with NTR; the hazard ratio decreased from 0.43 in Q1 to 0.16 in Q4. Conclusions DpR was strongly associated with OS in patients with NSCLC receiving first‐line platinum‐based therapy. Additional studies may help to define the role of DpR in solid tumors.

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The Value of Early Depth of Response in Predicting Long-Term Outcome in EGFR-Mutant Lung Cancer

Abstract: The PFS advantage of EGFR-TKI over chemotherapy in advanced EGFR mutant NCLC is not explained by depth of response at 6 or 12 weeks. It should not be used as a surrogate of benefit in future trials or routine clinical decision making.

Cited by 18 publications

References 36 publications

Larger tumors are associated with inferior progression‐free survival of first‐line EGFR‐tyrosine kinase inhibitors and a lower abundance of EGFR mutation in patients with advanced non‐small cell lung cancer

Larger tumors are associated with inferior progression‐free survival of first‐line EGFR‐tyrosine kinase inhibitors and a lower abundance of EGFR mutation in patients with advanced non‐small cell lung cancer

A novel imaging biomarker for survival prediction in EGFR-mutated NSCLC patients treated with TKI

Association between depth of response and survival in patients with advanced‐stage non–small cell lung cancer treated with first‐line chemotherapy

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