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Welcome to OncLive®’s OncFive!

Every week, we bring you a quick roundup of the 5 top stories from the world of oncology—ranging from pivotal regulatory decisions to key pipeline updates to expert insights on breakthroughs that are moving the needle in cancer care. This resource is designed to keep you informed on the latest updates in the space, in just a matter of minutes.

Here’s what you may have missed this week:

The FDA has approved lurbinectedin (Zepzelca) plus atezolizumab (Tecentriq) or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) as maintenance therapy for adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed following frontline induction therapy. This decision was supported by findings from the phase 3 IMforte trial (NCT05091567), which demonstrated significantly improved progression-free survival (PFS; median 5.4 vs 2.1 months; HR 0.54) and overall survival (median 13.2 vs 10.6 months; HR 0.73) with the combination vs atezolizumab alone. Among those with measurable disease, the confirmed overall response rate (ORR) was 19.4% with the lurbinectedin regimen vs 10.4% with atezolizumab monotherapy; the median duration of response was 9.0 months vs 5.6 months. Safety findings showed higher rates of adverse effects (AEs) with the combination, including nausea, anemia, fatigue, and thrombocytopenia, although most were manageable. Investigators highlighted that the combination represents a practice-changing option for eligible ES-SCLC patients with good performance status and appropriate hematologic parameters.

The FDA has accepted a supplemental biologics license application (sBLA) seeking approval of neoadjuvant fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) followed by docetaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP) in high-risk, HER2-positive, stage II/III breast cancer. This submission is based on data from the phase 3 DESTINY-Breast11 trial (NCT05113251), which indicated that neoadjuvant T-DXd followed by THP significantly improved pathologic complete response (pCR) rates vs dose-dense doxorubicin and cyclophosphamide followed by THP; early trends of improved event-free survival (EFS) with the regimen were also observed. Safety was consistent with known profiles, and rates of interstitial lung disease were comparable between the arms. The regulatory agency set a Prescription Drug User Fee Act target action date of May 18, 2026, and results are expected to be presented at an upcoming medical meeting.

The FDA is reviewing a biologics license application (BLA) seeking approval of pivekimab sunirine (IMGN632), an investigational antibody-drug conjugate (ADC), for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). The submission is based on findings from the phase 1/2 CADENZA trial (NCT03386513), which showed a composite complete response (cCR) rate of 75% in patients with first-line de novo BPDCN and an ORR of 80%. Across all first-line patients, the cCR rate and ORR were 70% and 85%, respectively. More modest activity was observed in those with relapsed/refractory disease, at a cCR rate of 14% and ORR of 35%. Key AEs comprised peripheral edema, infusion reactions, fatigue, gastrointestinal toxicities, and neutropenia, with grade 3 or higher effects reported in 79% of patients. No cases of capillary-leak syndrome were observed.

T-DXd significantly improved invasive disease-free survival (iDFS) vs ado-trastuzumab emtansine (T-DM1; Kadcyla) in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant therapy, according to data from a planned interim analysis of the phase 3 DESTINY-Breast05 trial (NCT04622319). Overall survival (OS) data remain immature, but the safety profile of the drug was consistent with prior studies, with no new AEs identified. This marks the second positive phase 3 trial of T-DXd in early-stage HER2-positive breast cancer following DESTINY-Breast11 (NCT05113251), which evaluated neoadjuvant T-DXd followed by THP. Results from both trials will be presented at the 2025 ESMO Congress and submitted to regulatory authorities, underscoring the ADC’s potential to optimize curative-intent therapy in high-risk HER2-positive early breast cancer.

In Q4, multiple FDA decisions could introduce new treatment options across solid tumors and hematologic malignancies. Recently, the regulatory agency approved lurbinectedin plus atezolizumab for first-line maintenance in ES-SCLC. Priority reviews are ongoing for cemiplimab-rwlc (Libtayo) in high-risk cutaneous squamous cell carcinoma, Dasynoc (XS004-dasatinib) for chronic myeloid leukemia/acute lymphoblastic leukemia, belantamab mafodotin-blmf (Blenrep)–based combinations in relapsed/refractory multiple myeloma, and more. These upcoming decisions reflect the evolving landscape of oncology treatment, with the potential to expand therapeutic options and improve patient outcomes in multiple cancer types. Sign up to access the full resource.

Honorable Mentions

• The FDA Report: Regulatory Rundown for September spotlights 4 key FDA approvals spanning urothelial cancer, NF-1–associated inoperable plexiform neurofibromas, solid tumors, and ESR1-mutated breast cancer.
• Ahead of the 2025 ESMO Congress, OncLive interviewed experts in lung cancer and gynecologic malignanciesto get their thoughts on which meeting abstracts they are most looking forward to learning more about. Sign up to access these exclusive preview articles.

Bitcoin BTC$121,856.93 has ripped about 13% this week, surging Friday to just shy of a new record of $124,500.

With that ceiling nearly cleared, a quick move to $135,000 could be in the cards, according to Standard Chartered head of digital asset research Geoffrey Kendrick.

In a note published on Friday, Kendrick argued that the U.S. government shutdown is playing a bigger role in markets than in past episodes supporting bitcoin’s rally. During the 2018-2019 shutdown, BTC traded in a different context. Now, the largest crypto has been closely correlated with U.S. government risk, measured by the U.S. Treasury term premiums, a relationship that suggests the uncertainty around the shutdown acts as a bullish driver this time.

Traders on prediction marketplace Polymarket currently give more than a 60% chance that the shutdown lasts 10–29 days. Kendrick forecasted BTC will continue to rise throughout that period.

Kendrick also highlighted a coming shift in ETF investor behavior. While gold ETFs have recently outperformed their BTC counterparts with gold pushing to record prices, spot bitcoin ETF flows are poised to catch up providing tailwind for the asset, the report said.

Of the $58 billion in net BTC ETF inflows so far, $23 billion has come in 2025, he said. This week alone, they attracted over $2.25 billion without the Friday session.

Kendrick projected that the vehicles could pull in another $20 billion investor capital by year-end – enough to keep his $200,000 year-end BTC price target in play.

Datacenters’ electricity demands have been accused of delaying the US’s transition to clean energy and requiring fossil fuel plants to stay online, while their high level of water consumption has also raised alarm. Now public health advocates fear another environmental problem could be linked to them – Pfas “forever chemical” pollution.

Big tech companies like Google, Microsoft and Amazon often need datacenters to store servers and networking equipment that process the world’s digital traffic, and the artificial intelligence boom is driving demand for more facilities.

Advocates are particularly concerned over the facilities’ use of Pfas gas, or f-gas, which can be potent greenhouse gases, and may mean datacenters’ climate impact is worse than previously thought. Other f-gases turn into a type of dangerous compound that is rapidly accumulating across the globe.

No testing for Pfas air or water pollution has yet been done, and companies are not required to report the volume of chemicals they use or discharge. But some environmental groups are starting to push for state legislation that would require more reporting.

Advocates’ concern increased in mid-September when the Environmental Protection Agency announced it would fast-track review of new Pfas and other chemicals used by datacenters. The datacenter industry has said the Pfas it uses causes minimal pollution, but advocates disagree.

“We know there are Pfas in these centers and all of that has to go somewhere,” said Jonathan Kalmuss-Katz, an attorney with the Earthjustice non-profit, which is monitoring Pfas use in datacenters. “This issue has been dangerously understudied as we have been building out datacenters, and there’s not adequate information on what the long term impacts will be.”

Pfas are a class of about 16,000 chemicals most frequently used to make products water-, stain- and grease-resistant. The compounds have been linked to cancer, birth defects, decreased immunity, high cholesterol, kidney disease and a range of other serious health problems. They are dubbed “forever chemicals” because they do not naturally break down in the environment.

Environmental advocates say the datacenters increase Pfas pollution directly and indirectly. The chemicals are needed in the centers’ operations – such as its cooling equipment – which almost certainly leads to some on-site pollution. Meanwhile, Pfas used in the equipment housed in the centers must be disposed of, which is difficult because the chemicals cannot be fully destroyed. Meanwhile, a large quantity of Pfas are used to produce the semiconductors housed in datacenters, which will increase pollution around supporting manufacturing plants.

The revelations come as the US seeks an edge over China as the industry leader in AI, and there has been little political interest in reining in the centers’ pollution.

“The US and China are racing to see who can destroy the environment most quickly,” said Lenny Siegel, a member of Chips Communities United, a group working with industry and administration officials to try to implement environmental safeguards. “If we had a sensible approach to these things then someone would have to present some answers before they develop and use these systems.”

Two kinds of cooling systems are used to prevent the semiconductors and other electronic equipment stored in datacenters from overheating. Water cooling systems require huge volumes of water, and chemicals like nitrates, disinfectants, azoles and other compounds are potentially added and discharged in the environment.

Many centers are now switching to a “two phase” system that uses f-gas as a refrigerant coolant that is run through copper tubing. In this scenario, f-gas is not intentionally released during use, though there may be leaks, and it must be disposed of at the end of its life.

The datacenter industry has claimed that f-gas that escapes is not a threat because, once in the air, it turns into a compound called Tfa. Tfa is considered a Pfas in most of the world, but not the US. Recent research has found it is more toxic than previously thought, and may impact reproductive systems similar to other Pfas.

Researchers in recent years have been alarmed by the ever-growing level of Tfa in the air, water, human blood and elsewhere in the environment. Meanwhile, some f-gases are potent greenhouse gases that can remain in the atmosphere for thousands of years. But f-gasses are lucrative for industry: about 60% of all Pfas manufactured from 2019 to 2022 were f-gas.

Different Pfas are also applied to datacenters’ cables, piping and electronic equipment. The chemicals are volatile, meaning they can simply move into the air from the equipment.

Meanwhile, any of that equipment or Pfas waste that is intentionally removed from datacenters either ends up in landfills, where it can pollute local waters, or is incinerated, according to industry documents. But incineration does not fully destroy Pfas compounds – it breaks them into smaller pieces that are still Pfas, or other byproducts with unknown health risks.

Datacenters are a “huge generator of electronic waste, with frequent upgrades to new equipment”, said Mike Belliveau, the founder of the Bend the Curve non-profit who has lobbied on toxic chemical legislation.

“The processing and disposal of electronic waste is a major source of global harm,” he added.

F-gas producer Chemours is using the boom in AI and datacenters as justification for increasing production at its Parkersburg, West Virginia, and Fayetteville, North Carolina, plants.

Both plants have been accused of polluting their regions’ water, soil and air, and poisoning drinking water. Residents in both regions say they’ve been sickened by Chemours’s pollution. Chemours’s expansion plans have been met with opposition over fears that its pollution will also increase.

A new coalition of Minnesota environmental groups is working with state lawmakers to develop legislation that would require companies to report on their use of Pfas and other chemicals in the cooling process.

Legislators in state hearings have asked tech companies which chemicals are used in datacenters and how they are disposed of, but “the answers are not satisfactory”, said Avonna Starck, Minnesota state director for Clean Water Action, which is spearheading the effort.

“There’s so much you just don’t know and we’re at the whim of these big corporations and what they’re willing to tell us,” Starck said. “We think the community has a right to know these things.”