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. 2017 Nov 1;28(11):2707-2714.
doi: 10.1093/annonc/mdx414.

Exploratory analysis of the association of depth of response and survival in patients with metastatic non-small-cell lung cancer treated with a targeted therapy or immunotherapy

C E McCoach  1 , G M Blumenthal  2 , L Zhang  3 , A Myers  2 , S Tang  3 , R Sridhara  3 , P Keegan  2 , R Pazdur  2 , R C Doebele  1 , D Kazandjian  2   4
Affiliations

Exploratory analysis of the association of depth of response and survival in patients with metastatic non-small-cell lung cancer treated with a targeted therapy or immunotherapy

C E McCoach et al. Ann Oncol. .

Erratum in

Abstract

Background: Response Evaluation Criteria in Solid Tumors (RECIST) permits rapid evaluation of new therapeutic strategies in cancer. However, RECIST does not capture the heterogeneity of response in highly active therapies. Depth of tumor response may provide a more granular view of response. We explored the association between, depth of response (DepOR), with overall survival (OS) and progression-free survival (PFS) for patients with NSCLC being treated with an ALK inhibitor (ALKi) or an anti-PD-1 antibody (Ab).

Methods: Experimental arms from two randomized controlled trials (RCTs) of an ALKi and two RCTs of an anti-PD-1 Ab were separately pooled. Patient responses were grouped into DepOR 'quartiles' by percentage of maximal tumor shrinkage (Q1 = 1%-25%, Q2 = 26%-50%, Q3 = 51%-75%, and Q4 = 76%-100%), Q0 had no shrinkage. We carried out a retrospective exploratory responder analysis to evaluate the association between DepOR and OS or PFS using hazard ratios (HR) generated by the Cox proportional hazards model.

Results: In the pooled ALK analysis there were 12, 39, 70, 144, and 40 patients in quartiles 0-4, respectively. The DepOR versus PFS/OS analyses HR were: 0.19/0.94 for Q1 0.11/0.56 for Q2, 0.05/0.28 for Q3, and 0.03/0.05 for Q4. In the PD-1 trials within quartiles 0-4 there were 168, 70, 44, 45, and 28 patients, respectively. The DepOR versus PFS/OS analyses HR were 0.3/0.52 for Q1, 0.22/0.47 for Q2, 0.09/0.07 for Q3, and 0.07/0.14 for Q4.

Conclusions: Our analysis suggests a greater DepOR is associated with longer PFS and OS for patients receiving ALKi or anti-PD1 Ab. Overall, this suggests that DepOR may provide an additional outcome measure for clinical trials, and may allow better comparisons of treatment activity.

Keywords: depth of response; immune therapy; non-small-cell lung cancer; response criteria; targeted therapy.

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Figures

Figure 1.
Figure 1.
(A) Waterfall plot of the pooled analysis of two ALK inhibitor trials depicting the maximum tumor shrinkage. (B) Kaplan–Meier curve for each quartile base on overall survival probability. (C) Kaplan–Meier curve for each quartile base on progression free survival probability. (D) Three-dimensional plot demonstrating DepOR, patient quartile (left figure), and median days on therapy for each quartile, days on therapy for the pooled ALKi trial patients. On the right, a 3D plot demonstrating DepOR, individual patient, and days on therapy for the pooled ALKi trial patients.
Figure 1.
Figure 1.
(A) Waterfall plot of the pooled analysis of two ALK inhibitor trials depicting the maximum tumor shrinkage. (B) Kaplan–Meier curve for each quartile base on overall survival probability. (C) Kaplan–Meier curve for each quartile base on progression free survival probability. (D) Three-dimensional plot demonstrating DepOR, patient quartile (left figure), and median days on therapy for each quartile, days on therapy for the pooled ALKi trial patients. On the right, a 3D plot demonstrating DepOR, individual patient, and days on therapy for the pooled ALKi trial patients.
Figure 2.
Figure 2.
(A) Waterfall plot of the pooled analysis of two PD-1 inhibitor trials depicting the maximum tumor shrinkage. (B) Kaplan–Meier curve for each quartile base on overall survival probability. (C) Kaplan–Meier curve for each quartile base on progression free survival probability in the two PD-1 inhibitor trials. (D) Three-dimensional plot demonstrating DepOR, patient quartile (left figure), and median days on therapy for each quartile, days on therapy for the pooled PD-1i trial patients. On the right, a 3D plot demonstrating DepOR, individual patient, and days on therapy for the pooled PD-1i trial patients.
Figure 2.
Figure 2.
(A) Waterfall plot of the pooled analysis of two PD-1 inhibitor trials depicting the maximum tumor shrinkage. (B) Kaplan–Meier curve for each quartile base on overall survival probability. (C) Kaplan–Meier curve for each quartile base on progression free survival probability in the two PD-1 inhibitor trials. (D) Three-dimensional plot demonstrating DepOR, patient quartile (left figure), and median days on therapy for each quartile, days on therapy for the pooled PD-1i trial patients. On the right, a 3D plot demonstrating DepOR, individual patient, and days on therapy for the pooled PD-1i trial patients.
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Comment in

References

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