soc-trials

AALL0232 showed that giving children with high-risk acute lymphoblastic leukaemia high doses of methotrexate with leucovorin rescue cured more of them than the older escalating schedule, and that the steroid dexamethasone helped children under ten but caused bone damage without benefit in older patients.

AALL1231 tried to improve treatment for T-cell leukaemia and lymphoma in children by adding bortezomib and by dropping routine radiotherapy to the brain; bortezomib clearly helped the lymphoma patients but not the whole group, and more than nine in ten children were spared cranial radiotherapy without more relapses.

AALL1331 tested swapping blocks of harsh chemotherapy for the antibody blinatumomab in children whose leukaemia had come back; the antibody caused far fewer serious infections, more patients survived in the higher-risk group, and children whose relapse was in the bone marrow did better in the low-risk group too.

AALL1521 is the trial that added the JAK-blocking pill ruxolitinib to chemotherapy for children whose leukaemia looks like Philadelphia-positive disease but is driven by JAK signalling; it has finished treating patients and the survival results are awaited.

AAML1031 was the children's leukaemia trial that found adding bortezomib to standard chemotherapy did not help and caused more nerve damage, while a separate part of the trial suggested that adding the FLT3 blocker sorafenib does improve outcomes for children whose leukaemia carries a high load of the FLT3-ITD mutation.

ACNS0121 showed that focused radiotherapy to the tumour bed straight after surgery cures most children with ependymoma, including those under three who used to be denied radiotherapy, and that children whose tumour could not be fully removed do far worse even with chemotherapy and a second operation.

ACNS0122 set the modern American standard for children with the more aggressive kind of germ cell tumour of the brain: chemotherapy first, surgery for anything left, then radiotherapy to the whole brain and spine, which cured about nine in ten and became the benchmark that later trials tried to match with less radiation.

ACNS0333 was the first trial built only for atypical teratoid/rhabdoid tumour, a brain cancer of very young children that used to be almost always fatal; its intensive plan of chemotherapy, high-dose chemotherapy with stem cell rescue and focused radiotherapy more than halved the risk of relapse or death compared with earlier treatment and became the template for care.

ACNS1123 asked whether children with germ cell tumours of the brain who respond well to chemotherapy can safely have less radiotherapy; for non-germinomatous tumours survival stayed high but the few relapses were all in the spine, which was left out of the smaller field, and for germinoma the reduced doses held.

ACNS1422 tests whether children with the WNT type of medulloblastoma, who almost always survive, can be given less radiotherapy to the brain and spine and less chemotherapy without more relapses; it has finished enrolling and the results are awaited.

ACTG A5263 tested whether two cheaper, easier chemotherapies could replace paclitaxel for people with HIV and advanced Kaposi sarcoma in Africa; both were clearly worse, so paclitaxel with antiretroviral therapy is the treatment to aim for wherever it can be supplied.

ADIUVO asked whether people whose low-grade adrenal cancer had been fully removed should take the toxic drug mitotane for two years to prevent recurrence; recurrence and survival were no different from watching and waiting, so observation with regular scans is the standard for this group.

ADIUVO-2 tests whether adding platinum chemotherapy to mitotane after surgery lowers the high relapse rate of aggressive adrenal cancers; it is still recruiting through MD Anderson and the ENSAT network.

AEWS0031 showed that giving the same chemotherapy for Ewing sarcoma every two weeks instead of every three cured more patients without adding side effects, and the two-weekly schedule became the standard for localised disease in North America.

AGCT1531 is testing two ways to spare people with germ cell tumours from long-term harm: watching low-risk patients after surgery and giving chemotherapy only if the tumour returns, and swapping cisplatin for carboplatin, which is kinder to hearing, in standard-risk disease; it is still recruiting.

AHOD1331 showed that replacing bleomycin with the antibody-drug conjugate brentuximab vedotin in the chemotherapy given to children and teenagers with advanced Hodgkin lymphoma cut relapses by more than half without extra side effects, and it became the new standard for high-risk disease.

ALL R3 found, to the investigators' surprise, that using mitoxantrone instead of idarubicin in the first block of treatment for children whose leukaemia had relapsed nearly doubled the chance of being alive without progression three years later, and mitoxantrone-based reinduction became the standard.

ANBL0531 showed that children with intermediate-risk neuroblastoma can be cured almost every time with a treatment plan that gives less chemotherapy to those with favourable tumour biology and a good early response, keeping three-year survival at 95 percent while cutting treatment for many.

ANBL1221 found that adding the anti-GD2 antibody dinutuximab to irinotecan and temozolomide shrank relapsed neuroblastoma in about half of children, while adding temsirolimus almost never did, and chemo-immunotherapy became the standard salvage treatment.

ANBL17P1 tested whether the antibody dinutuximab, which works against relapsed neuroblastoma, can be given from the very start of treatment alongside induction chemotherapy for newly diagnosed high-risk disease; none of the 42 children had unacceptable toxicity, which opened the way to the randomised trial now under way.

ANCHOR proved for the first time that treating precancerous anal lesions in people with HIV prevents anal cancer: those whose lesions were removed or ablated were 57 percent less likely to develop cancer than those who were simply monitored, which is the evidence behind screening and treating these lesions.

AURELIA showed that adding bevacizumab to single-drug chemotherapy for ovarian cancer that has stopped responding to platinum doubled the time before the cancer grew again, from 3.4 to 6.7 months, and more than doubled the response rate, though it did not clearly lengthen life.

BALLAD is the first randomised trial of chemotherapy after surgery for cancer of the small intestine, a rare tumour whose treatment has been borrowed from colon cancer; it tests both whether chemotherapy helps at all and whether adding oxaliplatin helps, and results are awaited.

BMT CTN 0803 showed that people living with HIV whose lymphoma had come back can have the same high-dose chemotherapy and stem cell transplant as anyone else, with 87 percent alive at one year and outcomes no different from matched HIV-negative patients, so HIV alone should not bar transplant.

BMT CTN 1102 settled whether older people with higher-risk myelodysplastic syndrome should be offered a stem-cell transplant: those who had a matched donor and went to transplant were far more likely to be alive three years later than those without a donor who had drug treatment instead, so transplant belongs in the plan for fit patients aged 50 to 75.

CAPP2 followed people with Lynch syndrome, an inherited condition that carries a very high risk of bowel cancer, for ten years after two to four years on aspirin or placebo: those who took aspirin developed about a third fewer bowel cancers, which is why daily aspirin is now offered to people with the syndrome.

CLASSIC showed that six months of capecitabine and oxaliplatin after a thorough stomach cancer operation stops the cancer returning in many more people, with 68 percent free of disease at five years against 53 percent with surgery alone, and more of them alive; it made CAPOX one of the two standard adjuvant treatments in East Asia.

CLL12 asked whether starting the pill ibrutinib early, before chronic lymphocytic leukaemia causes symptoms, is better than the usual practice of watching and waiting; early treatment delayed the disease but after nearly six years of follow-up people lived just as long either way, so watch and wait remains the standard.

COMFORT-I showed that the JAK-blocking pill ruxolitinib shrank the grossly enlarged spleens of people with myelofibrosis in about four in ten patients, against almost none on placebo, and eased their fatigue, night sweats and itching; it led to the first approved drug for the disease.

COMFORT-II was the European companion to COMFORT-I: ruxolitinib shrank the spleen by more than a third in 28 percent of people with myelofibrosis after nearly a year, while not one patient on the best treatment their doctor could otherwise offer achieved that, and symptoms and quality of life improved.

CONKO-001 was the trial that made chemotherapy after pancreatic cancer surgery routine: six months of gemcitabine doubled the time before the cancer came back and roughly doubled the share of patients alive at five years, from 10 to 21 percent.

CONTINUUM was the first trial to show that adding a PD-1 immunotherapy, sintilimab, to the chemotherapy and radiotherapy given for advanced but not yet metastatic nasopharyngeal cancer keeps more people free of relapse three years later, 86 against 76 percent, at the cost of more side effects.

DRAMMATIC asks two questions about maintenance treatment after a stem cell transplant for myeloma: whether adding daratumumab to lenalidomide helps people live longer, and whether those whose tests show no detectable disease after two years can safely stop; it is still running with about 1,100 patients.

ESPAC-3 compared the two adjuvant chemotherapies then available after pancreatic cancer surgery and found they gave the same survival, about 23 months, but gemcitabine caused half as many serious side effects; a companion cohort in ampullary and bile duct cancers is still the main randomised evidence for adjuvant chemotherapy in those rarer tumours.

ESPAC-4 showed that adding the tablet capecitabine to gemcitabine after pancreatic cancer surgery lengthened median survival from 25.5 to 28 months, and the pair became the adjuvant standard for people who cannot tolerate the harsher FOLFIRINOX regimen.

ESPAC-5 randomised people whose pancreatic cancer sat on the border of being removable between going straight to surgery and having two months of chemotherapy or chemoradiotherapy first; those treated first were far more likely to be alive a year later, 78 to 84 percent with chemotherapy against 39 percent with immediate surgery, which supports treating before operating in borderline disease.

EsPhALL is the European intergroup study that brought the leukaemia pill imatinib into treatment for children with Philadelphia-positive acute lymphoblastic leukaemia; the first version gave it in short bursts after induction and the second gave it continuously, and together they set the chemotherapy backbone that the standard of care still uses.

EuroNet-PHL-C2 is the huge European trial that treats children with Hodgkin lymphoma using PET scans after the first two cycles to decide who can skip radiotherapy, and tests a more intensive chemotherapy consolidation to make that possible for more of them; enrolment of nearly 3,000 children has closed and the full results are awaited.

EXPLORER was the first human study of avapritinib, a pill designed to block the KIT D816V mutation that drives almost every case of advanced systemic mastocytosis; three quarters of evaluable patients responded and a third went into complete remission, and the drug was approved for the disease in 2021.

FIRSTMAPPP was the first randomised trial ever completed in metastatic phaeochromocytoma and paraganglioma, rare hormone-producing tumours; the kinase inhibitor sunitinib kept 36 percent of patients free of progression at a year against 19 percent on placebo, giving the disease its first drug with randomised evidence.

FoRT asked whether two very small doses of radiotherapy control follicular lymphoma as well as the standard twelve; they do not, with about three times the rate of regrowth in the treated area, so 24 Gy stays the standard when the aim is lasting control and 4 Gy is kept for palliation.

GALLIUM showed that the newer anti-CD20 antibody obinutuzumab kept follicular lymphoma at bay for longer than rituximab when given with chemotherapy and as maintenance, at the cost of more serious side effects, and it became a first-line option.

GETUG 13 showed that men with the worst-risk testicular cancers whose tumour markers fall too slowly after the first cycle of chemotherapy do better if treatment is intensified: 59 percent were free of progression at three years against 48 percent with standard BEP, and fewer needed high-dose salvage chemotherapy.

GRAALL-2005 treated adults with acute lymphoblastic leukaemia using an intensive protocol borrowed from children's medicine and asked whether giving cyclophosphamide in a more intense split schedule helped; it did not, and the trial also showed that people aged 55 and over tolerate the paediatric-style treatment poorly.

IELSG32 built the MATRix regimen that is now the standard first treatment for lymphoma confined to the brain: adding rituximab and thiotepa to methotrexate and cytarabine doubled the complete remission rate, and its second part showed that a stem cell transplant works as well as whole-brain radiotherapy for consolidation, with less harm to thinking.

IMpactMF is the first myelofibrosis trial designed to prove that a drug helps people live longer rather than just shrinking the spleen; it compares the telomerase blocker imetelstat with the best treatment doctors can otherwise offer after a JAK inhibitor has stopped working, and results are expected towards 2028.

InPACT is the first international trial in penile cancer that has spread to the groin nodes; it tests whether chemotherapy or chemoradiotherapy before removing the nodes, and preventive removal of pelvic nodes afterwards, help people live longer, and it is the reason chemoradiotherapy is offered within the trial as an alternative to chemotherapy.

InterAACT was the first randomised trial ever run in advanced anal cancer; the two chemotherapy pairs shrank tumours equally often, but carboplatin with paclitaxel caused far fewer serious side effects and patients on it lived longer, so it became the standard chemotherapy backbone.

IntReALL SR 2010 brought the European relapse groups together to compare their two chemotherapy programmes head to head for children whose leukaemia had returned, and to test adding an antibody against CD22; it has completed and the corpus records the design while the full results are awaited.

INTUITT-NF2 is a rolling trial for people with the inherited condition NF2, who grow many benign tumours of the nerves and brain lining; its first drug, brigatinib, shrank a share of tumours, slowed the growth of all types and improved hearing in a third of affected ears, which is the evidence behind offering it for these tumours.

LAP07 tested whether adding radiotherapy after four months of chemotherapy helps people whose pancreatic cancer has not spread but cannot be removed; it did not lengthen life, although it did keep the tumour in check locally for longer, and adding erlotinib to gemcitabine did not help either.

MATRix/IELSG43 settled how to consolidate remission in lymphoma of the brain: after MATRix chemotherapy, a high-dose chemotherapy and stem cell transplant kept 78 percent of patients free of progression at three years against 51 percent with conventional consolidation chemotherapy, and also lengthened survival, so transplant is now the preferred consolidation for fit patients.

MORPHO asked whether taking the FLT3 blocker gilteritinib for two years after a stem-cell transplant keeps leukaemia from returning; across everyone the benefit fell just short of statistical proof, but in the half of patients whose blood tests still showed traces of leukaemia the drug clearly cut relapses.

NCI9673 was the first completed immunotherapy trial in anal cancer: nivolumab on its own shrank tumours in a quarter of heavily treated patients, which made PD-1 blockade a standard later option, but the follow-on randomisation showed that adding ipilimumab did not help and added toxicity.

NOA-08 showed that older people with glioblastoma can be treated with temozolomide tablets instead of six weeks of radiotherapy without living less long, and that the MGMT test tells you which to choose: chemotherapy if the gene is methylated, radiotherapy if it is not.

NORPACT-1 asked whether giving FOLFIRINOX chemotherapy before surgery helps people whose pancreatic cancer can be removed straight away; it did not, and patients who went straight to surgery were if anything more likely to be alive at 18 months, so upfront surgery remains the standard for clearly resectable disease.

POD1UM-303 showed that adding the immunotherapy retifanlimab to the standard carboplatin-paclitaxel chemotherapy for advanced anal cancer delayed progression by about two months in median terms and reduced the risk of progression by 37 percent, making it the first immunotherapy to improve first-line treatment of this cancer.

PRECEDE is a very large international study following people whose genes or family history put them at high risk of pancreatic cancer, with yearly scans and stored blood samples, to find out how to catch the cancer early enough to cure it; it is still enrolling towards 20,000 participants.

PTLD-1 established how to treat lymphoma that arises after an organ transplant: start with the antibody rituximab alone, and use how well the patient responds to decide whether to continue rituximab or move to chemotherapy; seven in ten reached complete remission and patients lived a median of more than six years.

QUAZAR AML-001 showed that a tablet form of azacitidine taken as maintenance after chemotherapy helped older people with acute myeloid leukaemia live about ten months longer than placebo, and it became the first approved maintenance treatment for the disease.