This Week in Oncology — Sep 9, 2026

Welcome to This Week in Oncology. This week we're covering 10 notable papers spanning targeted therapy in thoracic cancers, precision-guided treatment selection across molecularly defined groups, and next-generation antibody and cell therapies — plus one trial that finally tells us how to deliver exercise to men on hormone therapy. Let's dive in.

We start in the lung, where the New England Journal of Medicine reports the first substantial clinical experience with a pan-RAS inhibitor in non-small-cell lung cancer. RAS mutations, taken as a group, drive roughly 30 percent of non-small-cell lung cancer, and until now only the G12C subset has been reliably druggable. Arbour and colleagues enrolled 136 previously treated patients with advanced RAS-mutant disease into a phase 1-2 dose-escalation and expansion study of daraxonrasib, an oral inhibitor that binds the active, guanosine-triphosphate-bound form of both mutant and wild-type RAS isoforms in a tri-complex with cyclophilin A. At doses of 300 milligrams or less, objective responses were seen in about a third of patients, with 37 percent responding at the 300 milligram dose — a consistent signal across dose levels rather than a single favourable cohort [1]. The cost is real: essentially every patient had some adverse event, rash, diarrhoea, nausea, vomiting and mucositis each affected at least 30 percent, grade 3 or higher events occurred in just over half of patients, and there were four grade 5 events. A companion news analysis in Cancer Discovery places this in context, noting that daraxonrasib has already earned approval in pancreatic cancer and that a phase 3 lung trial is under way [2]. The practical message for now is that RAS genotyping in lung cancer should no longer stop at G12C — non-G12C RAS-mutant patients are becoming trial-eligible, and this is a referral conversation, not yet a prescription.

The Lancet, meanwhile, delivers a clearly negative result that should change what we offer earlier-stage patients. SWOG and NRG's S1914 trial randomised 402 eligible patients with medically inoperable or surgery-declining T1 to T3 node-negative non-small-cell lung cancer, all carrying at least one recurrence risk factor, to stereotactic body radiation alone or to the same radiation wrapped in up to eight cycles of neoadjuvant, concurrent and adjuvant atezolizumab. Accrual was stopped at the first interim analysis for futility. With nearly 25 months of median follow-up there was no survival separation whatsoever — the hazard ratio sat essentially at one, and estimated two-year overall survival was 82 percent in both arms. What did differ was toxicity: grade 3 or higher events rose from 3 percent with radiation alone to 12 percent with the combination, including two fatal respiratory events in the immunotherapy arm [3]. This is the first fully reported cooperative-group phase 3 trial of immunotherapy in inoperable early-stage disease, and it argues against extrapolating the stage 3 and adjuvant immunotherapy playbook into this population off-protocol. Rounding out the thoracic theme, a Lancet Series paper reviews the shifting landscape of small-cell lung cancer, where cell-surface target discovery is now driving T-cell engagers, antibody-drug conjugates, radioconjugates and cell therapies into the clinic in a disease that has resisted cytotoxics for decades [4].

Our second theme is molecularly guided treatment selection, and here two papers from different journals make complementary arguments. In the Journal of Clinical Oncology, Krämer and colleagues report updated results from CUPISCO, which randomised 436 patients with previously untreated unfavourable cancer of unknown primary — all of whom had achieved disease control after three cycles of induction platinum chemotherapy — three to one to molecularly guided therapy chosen by a molecular tumour board after comprehensive genomic profiling, versus three further cycles of chemotherapy. With 37 months of median follow-up, the genomically guided approach reduced the risk of progression by about a quarter, extending median progression-free survival from 4.4 to 6.1 months. Median overall survival was longer with molecular guidance, 15.2 versus 12.8 months, but that difference did not reach statistical significance, and no new safety signals emerged [5]. The honest reading is that these are modest absolute gains in a difficult disease, but the direction is consistent and it supports sending genomic profiling at the time of diagnosis rather than at progression, so that a guided option exists when induction chemotherapy runs out.

The Lancet Oncology takes the same principle into myeloma with the five-year follow-up of OPTIMUM, or MUKnine. This UK trial treated 107 patients with newly diagnosed high-risk myeloma — defined by two or more high-risk cytogenetic abnormalities, high-risk gene expression profiling, or plasma cell leukaemia — with intensified daratumumab-based quintuplet induction, transplant, extended two-part consolidation, and daratumumab-lenalidomide maintenance, and compared them with 120 molecularly matched patients from Myeloma XI. Median progression-free survival had not been reached in OPTIMUM versus 24 months in the external control, corresponding to roughly a two-thirds reduction in the risk of progression, and overall survival was also not reached versus 57 months in the control group. The benefit held across high-risk subgroups with one clear exception — patients carrying three or more high-risk cytogenetic abnormalities [6]. The design caveat matters: this is a non-randomised comparison against a historical cohort with far longer follow-up. But the effect size is large enough, and the subgroup consistency strong enough, to strengthen the case for upfront molecular risk stratification and for treating high-risk myeloma as a distinct disease requiring extended, intensified therapy.

Also in the Lancet Oncology, Vergote and colleagues report the final analysis of KEYLYNK-001, which enrolled 1,367 patients with stage 3 or 4 BRCA non-mutated epithelial ovarian cancer across 224 centres. Chemotherapy plus pembrolizumab followed by pembrolizumab-olaparib maintenance reduced the risk of progression by roughly a third compared with chemotherapy and placebo, both in the PD-L1-high population and in the intention-to-treat population, and that benefit was maintained at nearly 50 months of follow-up. Critically, pembrolizumab added to chemotherapy without olaparib was not significantly better than control [7]. So the signal here comes from adding a PARP inhibitor in maintenance in a BRCA wild-type population, not from checkpoint inhibition — a useful corrective for anyone tempted to read this as an immunotherapy win in ovarian cancer.

Our third theme is engineered antibodies and cell therapy. In JAMA Oncology, Li and colleagues report a Chinese phase 3 registrational trial in 521 patients with stage 2 or 3 ERBB2-positive breast cancer, comparing six cycles of neoadjuvant anbenitamab — a biparatopic HER2 antibody designed to cluster the receptor — plus albumin-bound docetaxel, against standard trastuzumab, pertuzumab and docetaxel, with carboplatin optional in both arms. Total pathological complete response rose from 51 percent to 62 percent, an absolute gain of about 11 points, with consistent direction across hormone receptor, stage and carboplatin subgroups, and grade 3 or 4 treatment-related adverse events essentially identical at around 29 percent in each arm with no treatment-related deaths [8]. That is a genuine challenge to the dual-antibody standard, though survival follow-up is pending and the trial was conducted entirely in China.

The same journal reports a phase 2 non-randomised trial of bicistronic CD19/CD22 CAR T-cells in 261 children with relapsed or refractory B-cell acute lymphoblastic leukaemia across five Chinese centres. Nearly every patient — 259 of 261 — achieved a minimal residual disease-negative complete remission, and event-free survival was 63 percent at two years and 62 percent at three years, with a median follow-up approaching three years. Consolidative transplant was associated with better event-free survival, 86 percent versus 58 percent at 24 months, and encouragingly, patients with isolated testicular or central nervous system relapse also did well. Grade 3 to 4 cytokine release syndrome affected just under half of patients, and neurotoxicity 13 percent [9]. Dual antigen targeting appears to address antigen-loss relapse, but this is single-arm data and the transplant comparison is not randomised.

Finally, supportive care. STAMINA, in the Lancet Oncology, randomised 700 men on androgen deprivation therapy for prostate cancer across 15 English National Health Service trusts to a twelve-month embedded programme of supervised aerobic and resistance exercise with dietary and behavioural support and gym membership, versus an optimised usual care arm that itself included clinician training, education and safety checks. At twelve months the intervention was superior on both primary outcomes — prostate-specific quality of life and fatigue — with a mean quality-of-life difference of about 4.5 points and a smaller fatigue benefit of just under 2 points. Three intervention-related serious adverse events occurred, all with recovery, and no treatment-related deaths [10]. The effect sizes are modest, and the cohort was 97 percent White, but this is the delivery model guidelines have been asking for.

If you only have time for one paper this week, make it STAMINA [10]. It is the only paper here that you can act on in clinic on Monday without a protocol, a genomic report, or a referral — it beat an actively optimised usual care arm, which is a harder comparator than most supportive care trials use.

Here are the key takeaways from this week in Oncology. First, RAS genotyping in lung cancer should extend beyond G12C, because a pan-RAS inhibitor is producing responses in about a third of previously treated patients and phase 3 testing is under way. Second, do not add atezolizumab to stereotactic radiation for inoperable early-stage lung cancer outside a trial — no survival benefit and four times the rate of severe toxicity. Third, order comprehensive genomic profiling at diagnosis in unfavourable cancer of unknown primary, and molecular risk stratification at diagnosis in myeloma, because both now have outcome data attached. Fourth, in BRCA wild-type ovarian cancer the progression benefit in KEYLYNK-001 tracks with olaparib maintenance, not with pembrolizumab alone. And fifth, prescribe supervised exercise for men on androgen deprivation therapy — there is now an implementable model with randomised evidence behind it.

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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