From the 2021 ASCO Annual Meeting

Abstract

0123456789();: Nature reviews | CliniCal OnCOlOgy The 2021 ASCO Annual Meeting, the 57th in the society’s history, was only the second to be held virtually. We at Nature Reviews Clinical Oncology — and undoubtedly many other delegates — miss the excitement and interactions that in-person meetings provide. Nevertheless, the apparently greater accessibility afforded by the online format seems highly relevant to the theme of the 2021 meeting. This year’s president, Lori J. Pierce, put equity at the forefront with the aim of including ‘Every patient. Every day. Everywhere.’, across all three pillars of ASCO’s mission — research, education and quality care. Hence, several sessions were devoted to identifying and addressing disparities in clinical oncology, for the benefit of not only under-represented and underserved groups but also the community as a whole. Besides socioeconomic, gender and ethnic disparities, the unmet therapeutic needs of particular patient subgroups were also addressed in research presented at the meeting. For example, the outcomes of patients with non-small-cell lung cancer (NSCLC) harbouring EGFR exon 20 insertions have lagged behind those with common exon 19 or 21 alterations, and the novel irreversible EGFR inhibitor DZD9008 was reported to produce an objective response rate (ORR) of 48% and a disease control rate (DCR) of 90% in this group. Most responses were ongoing, suggesting encouraging durability. In patients with EGFR-mutant NSCLC resistant to current EGFR inhibitors, the HER3targeted antibody–drug conjugate patritumab deruxtecan was associated with an ORR of 39%, a DCR of 72% and a median progression-free survival (PFS) of 8.2 months. In patients with osimertinib-resistant NSCLC, combination therapy with the anti-EGFR–MET bispecific antibody amivantamab and the third-generation EGFR inhibitor lazertinib resulted in an ORR of 36% and a median PFS of 4.9 months; these figures were 47% and 6.7 months in those with detectable osimertinib-resistance mutations, or EGFR and/or MET amplifications. With regard to EGFR-wildtype NSCLC, multiple phase III trials revealed that patients with resectable disease can benefit from immune-checkpoint inhibitors (ICIs). In CheckMate 816, addition of the anti-PD-1 antibody nivolumab to neoadjuvant chemotherapy increased the pathological complete response rate from 2.2% to 24.0% (P < 0.0001). Moreover, in the IMpower010 trial of the anti-PD-L1 antibody atezolizumab versus best supportive care after postoperative chemotherapy, the median disease-free survival (DFS) was 42.3 months versus 35.3 months in all randomized patients (P = 0.0205), with compar able results in the PD-L1+ subgroup. Updated data from the PACIFIC trial also underscore the benefit of durvalumab, another anti-PD-L1 antibody, after definitive chemoradiotherapy for patients with unresectable stage III NSCLC: 5-year PFS and overall survival (OS) of 33.1% and 42.9%, respectively, compared with 19.0% and 33.4% with placebo. Beyond NSCLC, adjuvant PD-1 blockade with pembrolizumab improved DFS in patients with renal cell carcinoma in the placebo-controlled, phase III KEYNOTE-564 trial (HR 0.68, 95% CI 0.53−0.87; P = 0.001). New data also suggest that additional frontline indications for anti-PD-1 antibodies in combina tion with chemotherapy for advancedstage cancers are on the horizon: both nivolumab and camrelizumab improved OS in patients with oesophageal squamous cell carcinoma included in CheckMate 648 and ESCORT-1st, respectively, and toripalimab prolonged PFS in patients with nasopharyngeal carcinoma involved in JUPITER-02. The novel ICI combination of relatlimab, an anti-LAG-3 antibody, and nivolumab also generated substantial interest, with efficacy seemingly similar to that of nivolumab plus ipilimumab in patients with both resectable (NCT02519322) and unresectable melanoma (RELATIVITY-047), but with a more favourable safety profile. In patients with ICI-refractory melanoma, the autologous tumour-infiltrating lymphocyte therapy lifileucel produced good results (ORR 36%; DCR 80%). Adoptive cell therapies for haematological cancers also featured prominently, including chimeric antigen receptor (CAR) T cells with targets distinct from those of currently approved products. Indeed, cell products targeting CLL1, CD7 or CD20 were associated with impressive efficacy in patients with acute myeloid leukaemia, T cell acute lymphoblastic leukaemia and anti-CD19 CAR T cell-refractory lymphomas, respectively. We look forward to hearing updates on these and many other innovative therapies in Chicago next year. The results of initiatives to ensure equal access are also eagerly awaited. David Killock in the news