ASCO 2023 Meeting Report — Lung Cancers

The 2023 American Society of Clinical Oncology (ASCO) annual meeting, held June 2 to 6 in Chicago, highlighted important advances in treatment across a broad spectrum of hematologic malignancies. Here, Associate Editor Dr. Jyoti Patel reviews several key trials in non–small-cell lung cancer.

Adjuvant treatment with osimertinib after resection of stage IB, II, or IIIA epidermal growth factor receptor (EGFR)–mutated non–small-cell lung cancer (NSCLC) significantly improves the chance of survival, regardless of whether patients received chemotherapy, according to the final overall survival (OS) analysis from the industry-sponsored, phase 3 ADAURA study (abstract LBA3 and N Engl J Med 2023 Jun 4; [e-pub]).

Researchers randomized 682 patients with completely resected EGFR-mutated NSCLC to receive the third-generation EGFR tyrosine kinase inhibitor osimertinib (80 mg daily) or placebo for 3 years; patients were allowed to receive adjuvant chemotherapy. The FDA approved adjuvant use of osimertinib in this patient population on the basis of the primary trial analysis showing a significant increase in disease-free survival.

In the current analysis, 5-year OS was significantly greater in the osimertinib arm than in the placebo arm (OS, 88% vs. 78%; hazard ratio for death, 0.49). This benefit was observed regardless of disease stage or receipt of adjuvant chemotherapy.

Summary by Cara Adler, Staff Writer

COMMENT — Dr. Jyoti Patel

We have witnessed significant advancements in the treatment of lung cancer over the past decade based on enhanced understanding of cancer biology. ADAURA unequivocally shows that osimertinib reduces the risk of death by over 50% in patients with resected EGFR-positive lung cancer. It is incumbent upon us now to ensure that we screen appropriate patients for lung cancer and perform adequate biomarker testing after diagnosis.

Neoadjuvant therapy with the immune checkpoint inhibitor pembrolizumab is associated with improved event-free survival in patients with early-stage non–small-cell lung cancer (NSCLC), according to the industry-supported, phase 3 KEYNOTE-671 trial (abstract LBA100 and N Engl J Med 2023 Jun 3; [e-pub]). Previous research has shown an event-free survival benefit with adjuvant pembrolizumab in early-stage NSCLC.

In the current trial, roughly 800 adults with previously untreated, resectable, stage II, IIIA, or IIIB (N2) NSCLC were randomized to receive neoadjuvant pembrolizumab (200 mg) or placebo plus cisplatin-based chemotherapy intravenously every 3 weeks for 4 cycles, followed by surgical resection and either adjuvant pembrolizumab or placebo for up to 13 additional cycles. The dual primary endpoints were event-free survival and OS.

In a prespecified interim analysis, estimated 24-month event-free survival was significantly improved with pembrolizumab, at 62% versus 41% in the placebo group. Estimated 24-month OS did not show a significant between-group difference at the time of the analysis (81% with pembrolizumab and 78% with placebo).

In addition, the major pathologic response rate was significantly greater with pembrolizumab than with placebo (30% vs. 11%), as was the pathologic complete response rate (18% vs. 4%). No new safety signals emerged.

Summary by Amy Herman, Staff Writer

COMMENT — Dr. Jyoti Patel

This study adds to the existing data regarding the benefit of checkpoint inhibition in resected NSCLC. However, it is difficult to delineate the benefit of preoperative, perioperative, or adjuvant pembrolizumab from this study. We await further analysis of overall survival as well as pathologic biomarkers of response and future therapy in this population.

Watch our interview with the lead author.

Adding pembrolizumab to chemotherapy does not significantly improve survival in patients with tyrosine kinase inhibitor (TKI)–resistant, EGFR-mutated, metastatic non–small-cell lung cancer (NSCLC), according to the industry-sponsored, phase 3 KEYNOTE-789 trial (abstract LBA9000).

Nearly 500 patients with EGFR-mutated NSCLC and disease progression after treatment with an EGFR TKI were randomized to receive either pembrolizumab or placebo with chemotherapy (pemetrexed with investigator's choice of carboplatin or cisplatin) every 3 weeks for 4 cycles, then with pemetrexed for another 31 cycles.

At the first interim analysis, at a median of 29 months, median progression-free survival, a coprimary endpoint, did not differ significantly between the pembrolizumab-chemotherapy and placebo-chemotherapy arms (5.6 and 5.5 months). At the final analysis, at a median of 42 months, overall survival, the other coprimary endpoint, was 87% and 91% in the two groups, respectively (hazard ratio, 0.84; P=0.0362), with a median OS of 15.0 and 14.7 months, respectively. The overall response rate was 29.0% with pembrolizumab chemotherapy and 27.1% with placebo chemotherapy, and median duration of response was 6.3 and 5.6 months, respectively.

The incidence of grade 3 or higher treatment-related adverse events was 44% in the pembrolizumab-chemotherapy arm and 39% in the placebo-chemotherapy arm; no new safety signals were identified.

Summary by Cara Adler, Staff Writer

COMMENT — Dr. Jyoti Patel

Despite the promise of immunotherapy in advanced NSCLC, it is clear that TKI-resistant, EGFR-mutant metastatic NSCLC derives less benefit from anti-PD1–based treatment than EGFR wildtype metastatic NSCLC. Biomarker assessment is needed to identify patients who may benefit more from other drug combinations or chemotherapy alone.