New Strategies Needed for Patients With NSCLC Who Progress on Chemoimmunotherapy

Results of a retrospective analysis showed modest efficacy with second-line chemotherapy, demonstrating the need for new combinations and strategies for patients with non–small cell lung cancer (NSCLC) who progress after first-line chemoimmunotherapy, according to study results presented at the 2022 World Conference on Lung Cancer.¹

The multicenter, international study analyzed outcomes of patients with advanced NSCLC who received first-line chemoimmunotherapy and received chemotherapy upon disease progression. The second-line treatment options included rechallenge with platinum-based chemotherapy (n = 11), a taxane with (n = 19) or without an anti-angiogenic (n = 49), or other chemotherapy regimen (n = 17; ie, gemcitabine, vinorelbine, pemetrexed).

Among 96 patients in the overall population the median progression-free survival (PFS) on second-line chemotherapy was 2.9 months (95% CI, 2.3-3.3) with a 6-month PFS rate of 18%. The median overall survival (OS) was 8.1 months (95% CI, 5.8-12.7) with a 6-month OS rate of 60%. The disease-control rate (DCR) was 38%.

The results were stratified by responders to first-line chemoimmunotherapy (n = 41)—defined as those who had a PFS lasting at least 6 months—and those with resistance to first-line therapy (n = 54)—defined as those who had a PFS of less than 6 months.

The median PFS and OS for the responder cohort was 3.2 months (95% CI, 2.9-5.8) and 12.7 months (95% CI, 8.1-not reached), respectively. The DCR was 50% and the 6-month PFS and OS rates were 23.3% and 81.0%, respectively.

Investigators noted that patients in the resistant cohort had worse outcomes with a DCR of only 27.5%. The median PFS was 2.4 months (95% CI, 1.7-3.0) with a 6-month PFS rate of 12.6%. The median OS and 6-month OS rate were 5.1 months (95% CI, 3.0-10.1) and 43.7%, respectively.

A total of 143 patients were identified as having received chemoimmunotherapy with documented disease progression. Among these patients, 125 were eligible for inclusion in the study after 16 patients were removed for receiving targeted therapy at disease progression. Further, for the presented analysis, 29 additional patients were excluded as they received treatment in the second-line setting with an agent other than chemotherapy. Treatment options included enrollment on a clinical trial (n = 12), immunotherapy (n = 8), other TKI (n = 5), or local treatment (n = 4).

Among the 96 patients included in the presented analysis, at baseline 47.9% of patients who received second-line chemotherapy were older than 65 years and 15.6% had squamous histology. Most patients (47.1d%) who had squamous histology received other chemotherapy drugs after progression. Further, 47.7% of patients had PD-L1–negative disease, 43.0% had PD-L1 expression 1% to 49%, and 9.3% of patients had PD-L1 expression greater than 50%. Twenty-nine patients had a KRAS mutation.

Metastatic disease was noted in the bone for 50% of patients, 14.6% had liver metastases, and 22.9% had brain metastases. Over 50% of patients had greater than 2 metastatic sites (51.1%). At the time of second-line therapy ECOG performance statuses were as follows: 0 (17.3%), 1 (36.5%), and 2 or 3 (46.1%).

Data were also reported for each second-line therapy among the responder and resistant cohorts.

Among patients in the responder cohort, 6-month PFS, 6-month OS, and DCR rates for those who received a taxane alone were 28.9%, 65.8%, and 31.6%, respectively. Among those who received a taxane with an anti-angiogenic the rates were 33.3%, 100%, and 60.0%, respectively. Patients who received either platinum-based chemotherapy or other chemotherapy also had a 6-month OS rate of 100%. The 6-month PFS rates were 20.0% and 16.7% for the 2 regimens, respectively, and the DCR rates were 83.3% and 66.7%.

“Rechallenge with platinum-based chemotherapy or taxane plus anti-angiogenic could be an option for selected patients, particularly in responders to [first-line treatment],” the study authors wrote.

For patients in the resistant cohort who received taxane monotherapy the 6-month PFS rate was 7.7%, the 6-month OS rate was 37.1%, and the DCR was 19.2%. Among those who received a taxane with an anti-angiogenic these rates were 31.2%, 41.7%, and 45.5%, respectively. Patients who received platinum-based chemotherapy had the best outcomes in this cohort with a 6-month PFS rate of 33.3%, a 6-month OS rate of 100%, and a DCR of 75%. Other chemotherapy options did not translate to a clinical benefit in terms of DCR (10%) or 6-month PFS rate (0%). The 6-month OS rate was 43.8%.

Reference

1. Auclin E, Benitez-Montanez J, Gorria T, et al. Second line treatment outcomes after progression on immunotherapy plus chemotherapy in non-small cell lung cancer. Presented at: International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Abstract OA07.06.