This Week in Oncology — Oct 28, 2026
Generated Oct 28, 2026 · 10:57
The week's practice-changing Oncology research, summarized for clinicians.
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Tarlatamab-Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer.
Adding tarlatamab to durvalumab maintenance extended median overall survival from about 13 to 21 months in extensive-stage small-cell lung cancer, with frequent but mostly low-grade cytokine release syndrome.
New England Journal of Medicine · 2026 · PubMed
This week’s papers
- 01
Tarlatamab-Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer.
Adding tarlatamab to durvalumab maintenance extended median overall survival from about 13 to 21 months in extensive-stage small-cell lung cancer, with frequent but mostly low-grade cytokine release syndrome.
Pérol M et al. · New England Journal of Medicine · 2026
From the briefingThe largest effect comes from DeLLphi-305, led by Pérol, which randomized 563 patients with extensive-stage small-cell lung cancer who had not progressed after initial chemoimmunotherapy to maintenance durvalumab with or without tarlatamab, the bispecific T-cell engager targeting DLL3 [1]. Median overall survival rose from about 13 months to about 21 months, and the risk of death fell by more than half; progression-free survival went from under two months to over seven. The price is real but mostly manageable: severe adverse events were modestly more frequent, and cytokine release syndrome occurred in nearly half of the patients receiving tarlatamab, mainly grade 1 or 2. This is an open-label interim analysis, but an overall survival primary endpoint with an effect this large is the kind of result that tends to reshape maintenance therapy.
If you only have time for one paper this week, make it DeLLphi-305 in the New England Journal of Medicine [1]. It is a rare overall survival win in extensive-stage small-cell lung cancer, a disease that has seen little progress, and it reopens the question of what first-line maintenance should look like.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 02
Divarasib as Compared with Sotorasib or Adagrasib in KRAS G12C-Mutated NSCLC.
Divarasib outperformed sotorasib or adagrasib in previously treated KRAS G12C-mutated lung cancer, improving progression-free and overall survival and response rates with fewer severe treatment-related adverse events.
Skoulidis F et al. · New England Journal of Medicine · 2026
From the briefingIn a second trial, Skoulidis and colleagues compared the next-generation KRAS G12C inhibitor divarasib against sotorasib or adagrasib in 338 previously treated patients with non-small-cell lung cancer [2]. Divarasib extended median progression-free survival by about four months, to just under ten, and improved overall survival, with response rates of roughly 58 versus 32 percent and fewer severe treatment-related adverse events. One nuance is that nearly all control patients received sotorasib, so the comparison with adagrasib rests on few patients.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 03
Osimertinib-Savolitinib in Advanced NSCLC after Progression during EGFR-TKI Therapy.
In EGFR-mutated lung cancer with MET overexpression or amplification after osimertinib progression, osimertinib plus savolitinib improved progression-free and overall survival versus platinum-pemetrexed with similar severe toxicity.
Lu S et al. · New England Journal of Medicine · 2026
From the briefingRounding out the lung theme, the SAFFRON trial led by Lu addressed MET-driven resistance after osimertinib [3]. Among patients with EGFR-mutated disease and MET overexpression or amplification, adding savolitinib to osimertinib was compared with platinum-pemetrexed. At one year, about a third of patients on the combination remained progression free, against one in ten on chemotherapy, and the risk of death fell by roughly a third. Peripheral edema affected about half of the patients on the combination, while severe adverse events were similar between arms. Notably, only about one in five screened patients were randomized, a reminder that this benefit applies to a biomarker-selected subgroup and depends on tissue testing for MET.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 04
Disease-free survival and overall survival after neoadjuvant immunotherapy in mismatch repair-deficient colon cancer in the Netherlands: results of the single-arm, multicentre, phase 2, NICHE-2 trial.
Brief neoadjuvant ipilimumab plus nivolumab in stage 2 or 3 mismatch repair-deficient colon cancer yielded 100 percent three-year disease-free and five-year overall survival in a single-arm trial.
Chalabi M et al. · The Lancet · 2026
From the briefingIn The Lancet, Chalabi and colleagues report long-term outcomes from NICHE-2, a single-arm Dutch phase 2 trial in which patients with stage 2 or 3 mismatch repair-deficient colon cancer received a single dose of ipilimumab and two doses of nivolumab before surgery [4]. Among 111 patients in the per-protocol population, three-year disease-free survival and five-year overall survival were both 100 percent. Circulating tumour DNA cleared before surgery in over four fifths of patients, and every patient was ctDNA negative after resection. The authors argue this supports neoadjuvant nivolumab plus ipilimumab as a potential standard of care, though it remains a single-arm study without a randomized comparator.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 05
Clinical Complete Response with Dostarlimab Monotherapy in dMMR/MSI-H Locally Advanced Rectal Cancer: First Results from the Global AZUR-1 Trial.
Dostarlimab alone produced a sustained 12-month clinical complete response in 68 percent of patients with mismatch repair-deficient locally advanced rectal cancer, with no recurrences among complete responders in interim analysis.
Cercek A et al. · Annals of Oncology · 2026
From the briefingIn rectal cancer, Annals of Oncology publishes the first results of the global AZUR-1 trial led by Cercek, testing nine cycles of dostarlimab alone in 154 patients with stage 2 or 3 mismatch repair-deficient locally advanced disease [5]. Roughly two thirds of evaluable patients achieved a clinical complete response sustained for 12 months, and no recurrences were reported among patients in clinical or pathological complete response, with severe immune-mediated adverse events in only 3 percent. This is an interim analysis, and central review lagged behind investigator assessment, but it strengthens the case for organ preservation without chemoradiation or surgery.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 06
Final results of nivolumab plus ipilimumab versus nivolumab or chemotherapy in microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer from CheckMate 8HW.
Nivolumab plus ipilimumab significantly improved overall survival versus nivolumab across lines and versus first-line chemotherapy in MSI-high metastatic colorectal cancer, though the first-line nivolumab comparison missed significance.
Lonardi S et al. · Annals of Oncology · 2026
From the briefingAlso in Annals of Oncology, Lonardi and colleagues present final overall survival from CheckMate 8HW in metastatic disease [6]. With nearly six years of median follow-up, nivolumab plus ipilimumab cut the risk of death by roughly 40 percent compared with nivolumab alone across all lines, and by close to two thirds versus first-line chemotherapy. The first-line comparison against nivolumab alone favoured the combination but did not meet its prespecified significance threshold, so the question of whether the doublet beats a single agent up front is suggestive rather than settled. Severe treatment-related events occurred in about a fifth of patients on the combination versus about one in seven on nivolumab.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 07
14-day versus 28-day trifluridine-tipiracil plus bevacizumab for refractory metastatic colorectal cancer (PRABITAS): a pragmatic, multicentre, open-label, randomised, phase 3, non-inferiority trial in Japan.
A simplified 14-day trifluridine-tipiracil plus bevacizumab schedule was non-inferior for overall survival in refractory metastatic colorectal cancer while cutting severe neutropenia from 39 to 13 percent.
Sakakida T et al. · The Lancet · 2026
From the briefingStaying with colorectal cancer but at the other end of the disease course, the PRABITAS trial in The Lancet, led by Sakakida, randomized 970 Japanese patients with refractory disease to trifluridine-tipiracil plus bevacizumab on the conventional 28-day schedule or a simplified 14-day schedule [7]. The 14-day schedule met non-inferiority for overall survival, with median survival around 11 months in both arms, while severe neutropenia dropped from roughly two in five patients to about one in eight, and anorexia also fell. Two treatment-related deaths occurred in the 14-day arm. The pragmatic design and broad eligibility make the result relevant to routine practice, though it was conducted entirely in Japan.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 08
Sacituzumab Tirumotecan plus Pembrolizumab in PD-L1-Negative Advanced NSCLC.
In PD-L1-negative nonsquamous lung cancer, sacituzumab tirumotecan plus pembrolizumab extended median progression-free survival to 15 months versus 5.7 with chemotherapy-pembrolizumab, while overall survival data remain immature.
Zhou F et al. · New England Journal of Medicine · 2026
From the briefingIn the New England Journal of Medicine, Zhou and colleagues report OptiTROP-Lung06, which randomized 455 patients with PD-L1-negative nonsquamous non-small-cell lung cancer without targetable alterations to the TROP2-directed conjugate sacituzumab tirumotecan plus pembrolizumab, or standard chemotherapy plus pembrolizumab [8]. Median progression-free survival rose from under six months to 15 months. Interestingly, response rates were nearly identical at around half of patients in each arm, but responses lasted about twice as long with the conjugate, and severe adverse events were actually less frequent, though stomatitis was common. Follow-up is short and overall survival is immature, so the survival signal remains preliminary.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 09
Trastuzumab Rezetecan in ERBB2-Low Advanced Breast Cancer: The HORIZON-Breast06 Randomized Clinical Trial.
Trastuzumab rezetecan more than doubled median progression-free survival versus chemotherapy in HER2-low metastatic breast cancer, regardless of hormone receptor status, but with higher rates of severe neutropenia.
Fan Y et al. · JAMA · 2026
From the briefingIn JAMA, the HORIZON-Breast06 trial led by Fan compared trastuzumab rezetecan with physician's choice of chemotherapy in 551 Chinese patients with HER2-low metastatic breast cancer and at most one prior chemotherapy line [9]. Median progression-free survival more than doubled, from about seven months to about 16, consistently across hormone receptor-positive and negative disease. Toxicity was substantial, however: severe treatment-related adverse events occurred in over four fifths of patients on the conjugate, driven by neutropenia, and overall survival was not reported.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 10
Durvalumab, Tremelimumab, and Enfortumab Vedotin in Muscle-Invasive Bladder Cancer.
For cisplatin-ineligible muscle-invasive bladder cancer, perioperative durvalumab with neoadjuvant enfortumab vedotin improved event-free and overall survival over cystectomy alone, at the cost of more severe adverse events.
Powles T et al. · New England Journal of Medicine · 2026
From the briefingMoving into the curative setting, the VOLGA trial led by Powles, also in the New England Journal of Medicine, enrolled cisplatin-ineligible patients with muscle-invasive bladder cancer [10]. Perioperative durvalumab with three cycles of neoadjuvant enfortumab vedotin raised two-year event-free survival from about 45 percent to about 64 percent versus cystectomy alone, and improved two-year overall survival by roughly nine points. Adding tremelimumab also improved event-free survival but brought more toxicity, and the two experimental arms were not compared directly. Severe adverse events occurred in over two thirds of patients in the durvalumab arms, compared with half in the surgery-alone arm, a trade-off that matters in an older, cisplatin-ineligible population.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
The full briefing
This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.
Welcome to This Week in Oncology. This week we're covering 10 notable papers spanning new targeted and immune strategies in lung cancer, immunotherapy for mismatch repair-deficient colorectal cancer, and antibody-drug conjugates moving into earlier lines of therapy. Let's dive in.
Lung cancer dominates the New England Journal of Medicine this week, with three phase 3 trials that each extend survival in a defined molecular or clinical niche. The largest effect comes from DeLLphi-305, led by Pérol, which randomized 563 patients with extensive-stage small-cell lung cancer who had not progressed after initial chemoimmunotherapy to maintenance durvalumab with or without tarlatamab, the bispecific T-cell engager targeting DLL3 [1]. Median overall survival rose from about 13 months to about 21 months, and the risk of death fell by more than half; progression-free survival went from under two months to over seven. The price is real but mostly manageable: severe adverse events were modestly more frequent, and cytokine release syndrome occurred in nearly half of the patients receiving tarlatamab, mainly grade 1 or 2. This is an open-label interim analysis, but an overall survival primary endpoint with an effect this large is the kind of result that tends to reshape maintenance therapy. In a second trial, Skoulidis and colleagues compared the next-generation KRAS G12C inhibitor divarasib against sotorasib or adagrasib in 338 previously treated patients with non-small-cell lung cancer [2]. Divarasib extended median progression-free survival by about four months, to just under ten, and improved overall survival, with response rates of roughly 58 versus 32 percent and fewer severe treatment-related adverse events. One nuance is that nearly all control patients received sotorasib, so the comparison with adagrasib rests on few patients. Rounding out the lung theme, the SAFFRON trial led by Lu addressed MET-driven resistance after osimertinib [3]. Among patients with EGFR-mutated disease and MET overexpression or amplification, adding savolitinib to osimertinib was compared with platinum-pemetrexed. At one year, about a third of patients on the combination remained progression free, against one in ten on chemotherapy, and the risk of death fell by roughly a third. Peripheral edema affected about half of the patients on the combination, while severe adverse events were similar between arms. Notably, only about one in five screened patients were randomized, a reminder that this benefit applies to a biomarker-selected subgroup and depends on tissue testing for MET.
Our second theme is mismatch repair deficiency in gastrointestinal cancer, where immunotherapy is steadily displacing chemotherapy, radiation, and in some cases surgery. In The Lancet, Chalabi and colleagues report long-term outcomes from NICHE-2, a single-arm Dutch phase 2 trial in which patients with stage 2 or 3 mismatch repair-deficient colon cancer received a single dose of ipilimumab and two doses of nivolumab before surgery [4]. Among 111 patients in the per-protocol population, three-year disease-free survival and five-year overall survival were both 100 percent. Circulating tumour DNA cleared before surgery in over four fifths of patients, and every patient was ctDNA negative after resection. The authors argue this supports neoadjuvant nivolumab plus ipilimumab as a potential standard of care, though it remains a single-arm study without a randomized comparator. In rectal cancer, Annals of Oncology publishes the first results of the global AZUR-1 trial led by Cercek, testing nine cycles of dostarlimab alone in 154 patients with stage 2 or 3 mismatch repair-deficient locally advanced disease [5]. Roughly two thirds of evaluable patients achieved a clinical complete response sustained for 12 months, and no recurrences were reported among patients in clinical or pathological complete response, with severe immune-mediated adverse events in only 3 percent. This is an interim analysis, and central review lagged behind investigator assessment, but it strengthens the case for organ preservation without chemoradiation or surgery. Also in Annals of Oncology, Lonardi and colleagues present final overall survival from CheckMate 8HW in metastatic disease [6]. With nearly six years of median follow-up, nivolumab plus ipilimumab cut the risk of death by roughly 40 percent compared with nivolumab alone across all lines, and by close to two thirds versus first-line chemotherapy. The first-line comparison against nivolumab alone favoured the combination but did not meet its prespecified significance threshold, so the question of whether the doublet beats a single agent up front is suggestive rather than settled. Severe treatment-related events occurred in about a fifth of patients on the combination versus about one in seven on nivolumab. Staying with colorectal cancer but at the other end of the disease course, the PRABITAS trial in The Lancet, led by Sakakida, randomized 970 Japanese patients with refractory disease to trifluridine-tipiracil plus bevacizumab on the conventional 28-day schedule or a simplified 14-day schedule [7]. The 14-day schedule met non-inferiority for overall survival, with median survival around 11 months in both arms, while severe neutropenia dropped from roughly two in five patients to about one in eight, and anorexia also fell. Two treatment-related deaths occurred in the 14-day arm. The pragmatic design and broad eligibility make the result relevant to routine practice, though it was conducted entirely in Japan.
Our final theme is antibody-drug conjugates replacing or joining standard therapy earlier in the disease course. In the New England Journal of Medicine, Zhou and colleagues report OptiTROP-Lung06, which randomized 455 patients with PD-L1-negative nonsquamous non-small-cell lung cancer without targetable alterations to the TROP2-directed conjugate sacituzumab tirumotecan plus pembrolizumab, or standard chemotherapy plus pembrolizumab [8]. Median progression-free survival rose from under six months to 15 months. Interestingly, response rates were nearly identical at around half of patients in each arm, but responses lasted about twice as long with the conjugate, and severe adverse events were actually less frequent, though stomatitis was common. Follow-up is short and overall survival is immature, so the survival signal remains preliminary. In JAMA, the HORIZON-Breast06 trial led by Fan compared trastuzumab rezetecan with physician's choice of chemotherapy in 551 Chinese patients with HER2-low metastatic breast cancer and at most one prior chemotherapy line [9]. Median progression-free survival more than doubled, from about seven months to about 16, consistently across hormone receptor-positive and negative disease. Toxicity was substantial, however: severe treatment-related adverse events occurred in over four fifths of patients on the conjugate, driven by neutropenia, and overall survival was not reported. Moving into the curative setting, the VOLGA trial led by Powles, also in the New England Journal of Medicine, enrolled cisplatin-ineligible patients with muscle-invasive bladder cancer [10]. Perioperative durvalumab with three cycles of neoadjuvant enfortumab vedotin raised two-year event-free survival from about 45 percent to about 64 percent versus cystectomy alone, and improved two-year overall survival by roughly nine points. Adding tremelimumab also improved event-free survival but brought more toxicity, and the two experimental arms were not compared directly. Severe adverse events occurred in over two thirds of patients in the durvalumab arms, compared with half in the surgery-alone arm, a trade-off that matters in an older, cisplatin-ineligible population.
If you only have time for one paper this week, make it DeLLphi-305 in the New England Journal of Medicine [1]. It is a rare overall survival win in extensive-stage small-cell lung cancer, a disease that has seen little progress, and it reopens the question of what first-line maintenance should look like.
Here is what this week's evidence adds up to in Oncology. First, tarlatamab-durvalumab maintenance substantially prolonged survival in extensive-stage small-cell lung cancer, though the data are interim and open-label and cytokine release syndrome is frequent. Second, in mismatch repair-deficient colorectal cancer, immunotherapy produced remarkable durability, with no recurrences in NICHE-2 and sustained complete responses in AZUR-1, but both are single-arm studies, and the first-line doublet-versus-monotherapy question in metastatic disease remains formally unresolved. Third, molecularly targeted strategies in lung cancer, whether a better KRAS G12C inhibitor or MET co-targeting after osimertinib, now carry overall survival evidence from randomized trials. Fourth, antibody-drug conjugates are showing large progression-free survival gains in first-line lung cancer, HER2-low breast cancer, and perioperative bladder cancer, with overall survival data immature or absent in two of the three and toxicity that varies widely. Finally, a simplified 14-day trifluridine-tipiracil schedule preserved survival with far less neutropenia, a pragmatic result from a single country.
That's your roundup for This Week in Oncology. The full transcript and references are available on the episode page. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.
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