ASCO 2026 Lung Cancer Abstracts: Clinical Practice Implications

Every ASCO Annual Meeting brings a wave of new data, but only a handful of abstracts truly shift how practice. Missak Haigentz, MD, chief of Thoracic Medical Oncology and chief of Head & Neck Medical Oncology, Rutgers Cancer Institute/Jack & Sheryl Morris Cancer Center, discusses the 3 abstracts he considers to be standouts from this year’s meeting.

LBA3: LIBRETTO-432 (Adjuvant Selpercatinib in RET Positive NSCLC)

LIBRETTO-432 (NCT04819100), presented as an ASCO plenary session abstract, is a study that shifts how we approach early-stage lung cancer.¹ This was a randomized phase 3 trial looking at adjuvant selpercatinib (Retevmo) in patients with completely resected RET fusion–positive non–small cell lung cancer (NSCLC) with stage IB to IIIA disease. The magnitude of benefit particularly in here was striking, with very significant improvement in event-free survival rates at 2 years, and although overall survival (OS) data is pending, it should be considered a new standard of care for this relatively uncommon genomic alteration (present in ~2% of NSCLC cases).

In this study it is important to note that although not mandated almost all stage II to IIIA patients on study received standard postoperative chemotherapy, so in the case of RET fusions, selpercatinib should not be thought of as a replacement for adjuvant chemotherapy.

RET has now joined EGFR and ALK as actionable targets for lung cancer in curative intent settings. As the growing number of actionable genomic targets with effective and tolerable therapies grow, the oncology scientific community will need to grapple on how to evaluate efficacy of interventions for other rare targets for which limited numbers of patients make large, randomized trials challenging.

From a practical standpoint, what this really means is that we have to start thinking differently about molecular testing in early-stage disease. Historically, comprehensive testing was reserved for advanced disease, but studies like this make it clear that we need to know the driver alterations upfront, even in patients we are treating with curative intent. For the community oncologist, that translates to making sure that next-generation sequencing (including detection of fusions) is part of the standard workflow, either at diagnosis or shortly after surgery. In clinic, this also raises important questions about long-term management. Patients may be on therapy for several years, so issues around tolerability, adherence, and monitoring become more important.

We will still want longer follow-up, but the signal is strong enough that this is very likely to change practice and guidelines quickly. Looking ahead, I think the next steps will involve integrating assays of circulating tumor DNA with ultrasensitive technologies to better identify who truly needs adjuvant therapy (and for those who have started therapy, possibly when it is safe to stop it) and exploring whether similar benefits can be achieved in the neoadjuvant setting. Overall, we are now in an era where early-stage lung cancer is being managed in a much more biology-driven way.

LBA8500: WU-KONG 28 (Sunvozertinib in EGFR Exon 20 Insertion Positive NSCLC)

The WU-KONG 28 study (NCT05668988) is important because it addresses a population we have struggled with for a long time, which is patients with EGFR exon 20 insertion mutations.² These tumors, unlike those with common EGFR mutations (eg EGFR L858R and EGFR exon 19 deletions) have responded poorly to earlier-generation EGFR inhibitors. This phase 3 trial showed that first-line treatment with sunvozertinib (Zegfrovy) improves outcomes compared to chemotherapy, with better progression-free survival (PFS) and a near doubling of response rates.

At a high level, the key takeaway is that this is now a targetable disease and targeted therapy works better than chemotherapy. However, in the US, the situation is a little more complex as our current practice has already evolved to include amivantamab (Rybrevant) in combination with first-line chemotherapy.

There are some practical considerations that come into play here. Sunvozertinib is an oral therapy, which is attractive for many patients, and there is now evidence that patients may avoid chemotherapy as an initial treatment. On the other hand, it is currently approved in the postplatinum setting, so access and reimbursement may limit how easily it can be used upfront. Furthermore, despite initial approval of sunvozertinib nearly a year ago, many US patients have experienced difficulty with accessing this agent due to production and supply chain issues. This creates a scenario where the data are ahead of real-world implementation.

Going forward, we need more data to guide sequencing decisions. Additional information on central nervous system activity and longer-term outcomes will also be helpful. Overall, this study is an important step forward, but its impact in practice will depend on how these questions are resolved.

Abstract 8506: OptiTROP-Lung05 (Sacituzumab Tirumotecan Plus Pembrolizumab)

OptiTROP-Lung05 (NCT06448312) is a study that really highlights where the field may be going next, particularly in patients without targetable mutations.³ This trial, performed in a Chinese population without EGFR or ALK alterations, evaluated the combination of sacituzumab tirumotecan (sac-TMT), an TROP2-directed antibody-drug conjugate (ADC), with pembrolizumab (Keytruda) compared with pembrolizumab alone in PD-L1–positive disease. The combination showed a clear improvement in PFS and response rates, regardless of tumor histology and PD-L1 extent of expression; interestingly, the benefit appeared more pronounced in patients with PD-L1 tumor proportion score (TPS) of 1 to 49% as compared to TPS ≥50%.

What is exciting here is the concept. For years, our backbone has been immunotherapy alone (primarily for PD-L1 TPS ≥50%), or immunotherapy combined with chemotherapy. This study suggests the possibility of replacing chemotherapy with ADCs in certain settings (perhaps best in low PD-L1 settings), which is a very appealing idea that needs clinical study.

At the same time, we have to be cautious in how we interpret these results. In current US practice, the standard for many patients involves immunotherapy plus traditional chemotherapy, and this trial did not directly compare against that regimen. In addition, the combination was associated with higher rates of hematologic toxicity, so tolerability will be an important consideration if this approach is adopted more broadly. And finally, PD-L1–negative patients for whom combination chemotherapy and immunotherapy are standard were not studied. For now, this is not ready to replace standard regimens in routine practice, but it does offer a glimpse into future treatment strategies.

Looking ahead, I think we will see more studies comparing ADC and immunotherapy combinations directly against immunotherapy plus chemotherapy, as well as efforts to better define which patients benefit most. Overall, this study represents an important step toward more effective and potentially less chemotherapy-dependent treatment approaches in lung cancer.

REFERENCES

1. Goldman J et al. Event-free survival with adjuvant selpercatinib in stage IB-IIIA RET fusion-positive NSCLC: Primary results of the phase 3 LIBRETTO-432 trial. J Clin Oncol. 44, 2026 (suppl 17; abstr LBA3). doi: 10.1200/JCO.2026.44.17_suppl.LBA3

2. Heymach J et al. Sunvozertinib monotherapy versus platinum-based chemotherapy as first-line treatment for advanced NSCLC with EGFR exon20ins: Primary analysis of a multinational phase 3 randomized study (WU-KONG28). J Clin Oncol. 44, LBA8500-LBA8500(2026).

DOI:10.1200/JCO.2026.44.17_suppl.LBA8500

3. Zhou C et al. Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (P) versus pembrolizumab (P) as first-line treatment for PD-L1–positive advanced non-small cell lung cancer (NSCLC): Results from the randomized phase 3 OptiTROP-Lung05 study. J Clin Oncol. 44, 2026 (suppl 16; abstr 8506). doi:10.1200/JCO.2026.44.16_suppl.8506