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

Abstract

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.

A narrative review: depth of response as a predictor of the long-term outcomes for solid tumors

“…For NSCLC, CA031 trial ( 36 ) divided patients into four groups based on the degree of DpR (Q1: >0% to 25%, Q2: >25% to 50%, Q3: >50% to 75%, Q4: >75%), and these 4 groups were compared with a group in which patients who had no tumor shrinkage or tumor enlargement. Results show that DpR is closely related to PFS and OS of NSCLC patients receiving first-line platinum-based chemotherapy ( Table 2 ) ( 37 ). Another retrospective analysis conducted by Qing et al also obtained similar results, in which advanced non-squamous non-small cell lung cancer patients received paclitaxel carboplatin combined with bevacizumab (TCBev) regimen as first-line chemotherapy ( 44 ).…”

Characterizing tumor shrinkage as a measure of clinical benefit for immune checkpoint inhibitors

“…14 Additionally, DepOR only measures the change in the sum of target lesions, but not non-target lesions, from baseline. 15 The clinical significance and adequacy of ORR as a surrogate for marketing approval (accelerated and regular) are dependent on other factors, including the DOR, DepOR, and complete response (CR) rates. 16 17…”

Metagenome association study of the gut microbiome revealed biomarkers linked to chemotherapy outcomes in locally advanced and advanced lung cancer

“…3,4 However, immunotherapy only has been reported to elicit durable responses in 20%-30% of patients, 5 and platinum-based chemotherapy is still the cornerstone treatment. 6 Despite continuous progress, the clinical outcomes of chemotherapy are still uneven and lack predictors. Early identification of patients who are sensitive or resistant to chemotherapy is very important to guide treatment and improve survival.…”

“…Revolutionary progress of immune checkpoint inhibitors has ushered in a new era of lung cancer treatment 3, 4 . However, immunotherapy only has been reported to elicit durable responses in 20%–30% of patients, 5 and platinum‐based chemotherapy is still the cornerstone treatment 6 . Despite continuous progress, the clinical outcomes of chemotherapy are still uneven and lack predictors.…”