This Week in Oncology — Aug 12, 2026

Welcome to This Week in Oncology. This week we're covering 9 notable papers spanning treatment intensification in advanced solid tumours, biomarker-guided and antibody-drug conjugate strategies, and the growing evidence base for supportive care and long-term survivorship. Let's dive in.

We start with intensification of first-line therapy, and the headline trial comes from The Lancet. PSMAddition randomised 1,144 men with PSMA-positive metastatic androgen pathway modulator-naive or sensitive prostate cancer across 169 sites and 20 countries to lutetium-177 PSMA-617, up to six cycles, added to androgen deprivation plus an androgen receptor pathway inhibitor, or to that hormonal backbone alone [1]. At the second interim analysis, with a median follow-up of just under 20 months, radiographic progression or death had occurred in roughly a quarter of the radioligand arm versus about 30 percent of controls, a 28 percent relative reduction in risk that met the primary endpoint, though median radiographic progression-free survival was not reached in either arm. This is a high-volume, largely de novo metastatic population — around two thirds had high-volume disease. The cost is toxicity: grade 3 or worse adverse events in about half the radioligand patients versus 43 percent of controls, and dry mouth in nearly half the treated men compared with 4 percent. Overall survival is not yet mature, and crossover was permitted, so the practical question for tumour boards is whether a progression-free survival gain of this magnitude justifies moving radioligand therapy from the castration-resistant setting into hormone-sensitive disease before we see survival data. In JAMA, a Chinese multicentre phase 3 trial took a different route to intensification — using a biomarker to select who needs more therapy [2]. Two hundred and ninety-four treatment-naive patients with EGFR-mutant advanced non-squamous lung cancer who also carried a TP53 mutation were randomised to osimertinib alone or osimertinib plus pemetrexed and carboplatin followed by maintenance. Median progression-free survival more than doubled, from 15.6 months to 34.0 months, a 56 percent reduction in the risk of progression, with benefit holding in those with brain metastases and L858R mutations. Grade 3 or higher treatment-related events were more common with chemotherapy, and overall survival is only about 30 percent mature with a trend favouring the combination. That poor 15.6-month result on osimertinib monotherapy is itself informative — it tells you TP53 co-mutation marks a genuinely higher-risk group, and it gives you a rational way to decide which EGFR-mutant patients to burden with platinum doublet up front.

Not every intensification strategy works, and Annals of Oncology delivers a clear negative. SKYSCRAPER-03 tested the anti-TIGIT antibody tiragolumab plus atezolizumab against durvalumab as consolidation after concurrent chemoradiation in unresectable stage III non-small cell lung cancer, randomising more than 800 patients [4]. In the PD-L1-positive primary population, median progression-free survival was 19.4 months with the combination versus 16.6 months with durvalumab, but the hazard ratio was 0.96 and the p value 0.76 — the primary endpoint was not met. Overall survival was also flat, with hazard ratios essentially at one in both the PD-L1-positive and all-comer populations. The combination was tolerated but offered nothing over durvalumab, and this adds to the accumulating disappointment around TIGIT blockade. Durvalumab remains the standard of care after chemoradiation. Set against that, also in Annals of Oncology, five-year follow-up from CheckMate 648 in advanced oesophageal squamous cell carcinoma shows durability where it exists [5]. Among 970 patients, both nivolumab plus chemotherapy and nivolumab plus ipilimumab maintained a roughly 38 percent reduction in the risk of death versus chemotherapy alone in tumours with PD-L1 expression of at least 1 percent, and about a 23 percent reduction across all randomised patients. Importantly, the progression-free survival benefit was seen only with nivolumab plus chemotherapy; the nivolumab-ipilimumab arm showed no progression-free survival advantage, with a hazard ratio just above one. Grade 3 or 4 treatment-related toxicity was highest with nivolumab plus chemotherapy at 49 percent, versus 33 percent for the dual immunotherapy arm. So the chemotherapy-free option remains reasonable for patients who cannot tolerate platinum, but you should counsel them that early progression risk is not reduced.

Turning to antibody-drug conjugates and local immunotherapy, the Journal of Clinical Oncology reports a biomarker-stratified phase 2 trial of trastuzumab rezetecan, a HER2-directed antibody-drug conjugate, in advanced salivary gland carcinoma — a disease with almost no prospective systemic data [7]. Among 46 patients, the confirmed objective response rate was 91.7 percent in the HER2-high cohort, including four complete responses, with median progression-free and overall survival not reached. In the HER2-low cohort, defined as immunohistochemistry 1+ or 2+ without amplification, the response rate was 45.5 percent, with median progression-free survival of 12.7 months and overall survival of 21.3 months. Grade 3 or higher treatment-related events occurred in about 41 percent, mostly neutropenia, and all interstitial lung disease was grade 1. These are single-arm, small cohorts, but the message is practical: test salivary gland carcinomas for HER2, including low-level expression. Also in the Journal of Clinical Oncology, updated results from the PIVOTAL phase 3 trial of neoadjuvant intralesional daromun — a combination of two antibody-cytokine fusion proteins — in 256 patients with fully resectable stage III melanoma [3]. At a median follow-up of nearly 37 months, the previously reported 41 percent reduction in the risk of recurrence with intralesional therapy before surgery versus up-front surgery was confirmed, along with improved distant metastasis-free survival and consistent post hoc event-free survival analyses, with no new safety signals. Note that 87 percent of enrolled patients had recurrent disease after prior surgery, so this is not a straightforward substitute for the neoadjuvant pembrolizumab approach in treatment-naive stage III disease.

Finally, two papers on supportive care and survivorship. In JAMA Oncology, a randomised trial across 52 German breast cancer centres enrolled 924 women with metastatic breast cancer on systemic therapy to weekly smartphone-based patient-reported outcome monitoring with automated alerts triggering a nurse or physician phone call within 48 hours, versus usual care with quarterly questionnaires [6]. At six months, fatigue scores were 5.4 points lower in the intervention arm, comfortably exceeding the minimal clinically important difference, and physical functioning was also meaningfully better; the difference in overall quality of life was small and below the clinically important threshold. One caveat: baseline fatigue was significantly worse in the control group, so some of the gap may reflect imbalance rather than intervention. Still, this supports building alert-based symptom monitoring into routine practice rather than treating it as a research add-on. And from the Children's Oncology Group in the Journal of Clinical Oncology, pooled echocardiographic data from 895 doxorubicin-treated children, about half randomised to dexrazoxane, with a mean follow-up of nearly six years [8]. Dexrazoxane was associated with better preserved left ventricular systolic function and roughly a 40 to 46 percent lower hazard of reduced left ventricular function beyond one and five years from diagnosis. Notably, among patients current guidelines classify as high risk, dexrazoxane reduced the incidence of reduced left ventricular function from 40 to about 22 events per thousand person-years — bringing them close to lower-risk rates and raising the question of whether dexrazoxane exposure should modify long-term cardiomyopathy screening intervals. Rounding out the week, a Journal of Clinical Oncology review on relapsed or refractory chronic lymphocytic leukaemia offers a practical sequencing framework after frontline covalent BTK inhibitors or fixed-duration venetoclax, covering second-generation covalent inhibitors, pirtobrutinib after prior exposure, lisocabtagene maraleucel in heavily pretreated disease, and the need to exclude Richter transformation at relapse [9].

If you only have time for one paper this week, make it the PSMAddition trial in The Lancet [1]. It is the first phase 3 evidence for moving PSMA-directed radioligand therapy into hormone-sensitive metastatic prostate cancer, and it will shape referral pathways and nuclear medicine capacity planning even before survival data mature.

Here are the key takeaways from this week in Oncology. Adding lutetium-177 PSMA-617 to androgen deprivation plus an androgen receptor pathway inhibitor delays radiographic progression in PSMA-positive hormone-sensitive prostate cancer, at the cost of more grade 3 toxicity and near-universal dry mouth, with survival data still pending. TP53 co-mutation identifies EGFR-mutant lung cancer patients who do poorly on osimertinib alone and who gained more than eighteen months of progression-free survival from added chemotherapy. Tiragolumab plus atezolizumab failed to beat durvalumab after chemoradiation in stage III lung cancer, so consolidation durvalumab stands unchanged. At five years in oesophageal squamous cell carcinoma, both nivolumab-containing regimens preserve a survival advantage, but only the chemotherapy combination improves progression-free survival. Test advanced salivary gland carcinoma for HER2, including HER2-low, given response rates above 90 percent in HER2-high disease with trastuzumab rezetecan. And dexrazoxane's cardioprotection in childhood cancer survivors persists long term and may justify rethinking screening intensity in those otherwise labelled high risk.

That's your roundup for This Week in Oncology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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