Adding Immunotherapy to Chemo Improves Survival in Metastatic Non-Small Cell Lung Cancer

The following article features coverage from the IASLC 2021 World Conference on Lung Cancer. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Adding durvalumab and tremelimumab to chemotherapy improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic, nonsquamous non-small cell lung cancer (NSCLC), phase 3 trial results suggest.

The results, from the POSEIDON trial (ClinicalTrials.gov Identifier: NCT03164616), were presented at the IASLC 2021 World Conference on Lung Cancer (WCLC) by Melissa Johnson, MD, of Sarah Cannon Research Institute in Nashville, Tennessee.

In the POSEIDON trial, researchers are evaluating the safety and efficacy of adding durvalumab, with or without tremelimumab, to a chemotherapy regimen in patients with treatment-naïve, metastatic NSCLC.

Patients are randomly assigned to receive 6 cycles of investigators’ choice of chemotherapy alone, 4 cycles of durvalumab with chemotherapy (DC), or 4 cycles of durvalumab, tremelimumab, and chemotherapy (DTC).

Chemotherapy regimens include gemcitabine plus carboplatin/cisplatin for patients with squamous cell histology, pemetrexed plus carboplatin/cisplatin for patients with nonsquamous cell histology, and nab-paclitaxel plus carboplatin for either histology.

After completing induction, patients proceed to maintenance with pemetrexed in the chemotherapy-alone arm, durvalumab plus pemetrexed in the DC arm, and durvalumab, tremelimumab, and pemetrexed in the DTC arm.

Overall Results

Dr Johnson presented data on 337 patients in the chemotherapy-alone arm, 338 in the DC arm, and 338 in the DTC arm.

The median age was 64 years in the chemotherapy arm, 64.5 years in the DC arm, and 63 years in the DTC arm. Most patients were men (73.6%, 74.9%, and 79.6%, respectively), and most had nonsquamous histology (63.5%, 61.8%, and 63.3%, respectively).

PFS was significantly improved in the DC and DTC arms, compared with the chemotherapy-alone arm.

The median PFS was 4.8 months in the chemotherapy arm, 5.5 months in the DC arm (hazard ratio [HR] vs chemotherapy, 0.74; 95% CI, 0.62-0.89; P =.0009), and 6.2 months in the DTC arm (HR vs chemotherapy, 0.72; 95% CI, 0.60-0.86; P =.0003).

Compared with the chemotherapy arm, OS was significantly improved in the DTC arm but not in the DC arm.

The median OS was 11.7 months in the chemotherapy arm, 13.3 months in the DC arm (HR vs chemotherapy, 0.86; 95% CI, 0.72-1.02; P =.076), and 14.0 months in the DTC arm (HR vs chemotherapy, 0.77; 95% CI, 0.65-0.92; P =.003).

Grade 3-4 treatment-related adverse events occurred in 44.4% of patients in the chemotherapy arm, 44.6% of those in the DC arm, and 51.8% of those in the DTC arm. Fatal treatment-related adverse events occurred in 2.4%, 2.1%, and 3.3% of patients, respectively.

Nonsquamous Histology

Dr Johnson noted that, among patients with nonsquamous histology, PFS and OS were longer with immunotherapy plus chemotherapy vs chemotherapy alone.

“And similar to the intent-to treat population, the benefit was greater for patients treated with durvalumab plus tremelimumab plus chemotherapy, for both PFS and overall survival,” she said.

The median PFS was 5.5 months in the chemotherapy arm, 6.4 months in the DC arm (HR vs chemotherapy, 0.77; 95% CI, 0.61-0.96), and 6.8 months in the DTC arm (HR vs chemotherapy, 0.66; 95% CI, 0.52-0.84).

The median OS was 13.1 months in the chemotherapy arm, 14.8 months in the DC arm (HR vs chemotherapy, 0.82; 95% CI, 0.66-1.03), and 17.2 months in the DTC arm (HR vs chemotherapy, 0.70; 95% CI, 0.56-0.87).

Squamous Histology

Among patients with squamous histology, PFS and OS were “poor across all treatment arms, with little separation of the curves for PFS or overall survival,” Dr Johnson said.

The median PFS was 4.6 months in the chemotherapy arm, 4.7 months in the DC arm (HR vs chemotherapy, 0.68; 95% CI, 0.52-0.90), and 4.6 months in the DTC arm (HR vs chemotherapy, 0.77; 95% CI, 0.58-1.01).

The median OS was 10.5 months in the chemotherapy arm, 11.5 months in the DC arm (HR vs chemotherapy, 0.84; 95% CI, 0.64-1.10), and 10.4 months in the DTC arm (HR vs chemotherapy, 0.88; 95% CI, 0.68-1.16).

Disclosures: This research was supported by AstraZeneca. Dr Johnson declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 

Read more of Cancer Therapy Advisor’s coverage of WCLC 2021 by visiting the conference page.

Reference

Johnson ML, Cho BC, Luft A, et al. Durvalumab ± tremelimumab + chemotherapy as first-line treatment for mNSCLC: results from the phase 3 POSEIDON study. Presented at: IASLC 2021 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 8-14, 2021; Abstract PL02.01.

This article originally appeared on Cancer Therapy Advisor