Adjuvant trials suggest changes to non-small cell lung cancer treatment paradigm: Results from clinical trials presented at the 2021 annual meeting of the American Society of Clinical Oncology may point to new ways to improve individualized therapy.

Abstract

At the 2021 annual meeting of the American Society of Clinical Oncology, positive data from several phase 3 clinical trials indicated an earlier role for novel therapeutic treatments for patients with metastatic disease. The studies suggest that adjuvant therapy with newer agents may increase disease-free survival in a range of tumor types and benefit select subsets of patients with a higher risk of recurrence after primary treatment. The results of 4 clinical trials in total were presented; they investigated adjuvant treatment versus placebo or best supportive care in resected renal cell carcinoma, locally advanced cervical cancer, early-stage non–small cell lung cancer (NSCLC), and BRCA1/2-mutant, HER2-negative early breast cancer.1 Among the trials that were presented, data from the OlympiA trial (ClinicalTrials.gov identifier NCT02032823) regarding the use of olaparib (Lynparza), a poly(adenosine diphosphate ribose) polymerase inhibitor, revealed that the invasive (3-year) diseasefree survival rate improved to 85.9% (in contrast to 77.1% with a placebo) for patients with HER2-negative breast cancer and a BRCA1/2 mutation present (hazard ratio [HR] 0.58; 99.5% CI, 0.41-0.82; P < 0.0001). These patients were considered to have a high risk of recurrence after initial local treatment and neoadjuvant/adjuvant therapy.1, 2 The KEYNOTE-564 trial (ClinicalTrials.gov identifier NCT03142334) showed an estimated disease-free survival rate of 77.3% with the use of pembrolizumab (Keytruda), a PD-1 inhibitor (in contrast to 68.1% with a placebo), in patients with clear cell renal cell carcinoma. The patients studied were categorized as intermediate high risk or high risk for recurrence after nephrectomy. A trend suggesting a 96.6% overall survival benefit with pembrolizumab versus a placebo (93.5%) was also noted by investigators.1, 3 Negative trial data from patients with advanced cervical cancer and a high rate of potential relapse were also discussed during the plenary session. Data from the OUTBACK trial (ACTRN12610000732088) illustrated similar progressionfree survival rates (63% vs 61%; 95% CI, -5 to +9; P = 0.61) without improved overall survival (72% vs 71%; 95% CI, -6 to +7; P = 0.91) at 5 years for patients with advanced cervical cancer who were given adjuvant chemotherapy after the administration of cisplatin-based chemoradiation.1, 4 IMpower010 (ClinicalTrials.gov identifier NCT02486718), a randomized, global, open-label trial of atezolizumab (Tecentriq), an anti–PD-L1, versus best supportive care after adjuvant treatment, studied patients with resected stage IB to IIIA NSCLC. A total of 1280 patients were enrolled; they received 4 cycles of cisplatin with vinorelbine, docetaxel, pemetrexed, or gemcitabine. Patients were randomized to receive 16 cycles of atezolizumab every 3 weeks or best supportive care. Those enrolled in the atezolizumab arm were given a median of 16 doses with periodic radiologic imaging; cycles in both phases lasted for 21 days.5 The primary results of the IMpower010 study illustrated a disease-free survival benefit with adjuvant atezolizumab after adjuvant chemotherapy in the PD-L1 TC ≥1% stage II-IIIA (stratified HR 0.66; P = 0.0039) and all randomized stage II-IIIA populations (stratified HR 0.79; P = 0.0205). Although adverse events of any grade occurred in 92.7% of the patients in the atezolizumab arm, the discontinuation rate in this population was 18.2%, and the safety profile was similar to that of prior use of atezolizumab as a monotherapy. Specific adverse events were not detailed in the published abstract results.5 Suresh S. Ramalingam, MD, of the Winship Cancer Institute at Emory University in Atlanta, Georgia, gave a virtual interview to CancerNetwork (https://www.cancernetwork.com/) related to the American Society of Clinical Oncology plenary session. “The notion that we could use immune checkpoint inhibitors in early-stage disease to improve overall outcomes is very exciting and an important step forward in the management of early-stage lung cancer.” —Suresh S. Ramalingam, MD Conversely, tailoring treatment interventions in the adjuvant setting may also dictate that some patients will do best by avoiding more toxic treatments. Placing an emphasis on improved outcomes for patients who face a possibly increased residual risk after their initial treatment highlights the importance of the comprehensive selection and strategy of therapy in the adjuvant care setting.