The Consequences of Withdrawing Oncology Drugs After Approval and Its Impact on Patient Care
- Dowdy Jackson
- 7 days ago
- 13 min read
The push to get promising drugs to patients as quickly as possible, while addressing potential safety concerns, led to the formation of the FDA's accelerated approval program, which was established in 1992.
Congress passed the US Food and Drug Administration (FDA) Amendments Act of 2007 to address potential safety concerns that can arise after a drug has received accelerated approval. In order to ensure compliance, the FDA could impose civil monetary penalties of up to $10 million on drug manufacturers that do not comply with the post-marketing requirements for confirmatory trials. It isn't clear if the FDA has actually fined a company for non-compliance.
The FDA's accelerated approval program states that a drug may be approved based on the use of biomarkers or surrogate endpoints, such as tumor shrinkage or radiographic images, that provides evidence that the drug may have significant clinical benefit for patients. As part of the accelerated approval, companies are required to perform additional clinical trials (post market approval clinical trials) that confirm the drug has clinical benefit to patients such as an increase in the patient survival rates.
The approval of oncology drugs often brings hope to patients and healthcare providers alike. These medications can offer new treatment options for cancers that previously had limited or no effective therapies. Yet, sometimes, drugs that receive initial approval are later withdrawn after post-market clinical trials reveal new information. This process raises critical questions about patient safety, regulatory oversight, and the future of cancer treatment. Understanding why oncology drugs are withdrawn and how this affects patient care is essential for patients, clinicians, and policymakers.
Why Oncology Drugs Are Withdrawn After Approval
Oncology drugs may be withdrawn or are no longer viable options for specific cancer patients for several reasons, often related to new data emerging from post-market clinical trials or real-world use. These reasons include:
Safety Concerns: Some drugs show unexpected side effects or toxicities that outweigh their benefits when used in a broader patient population.
Lack of Efficacy: Initial trials may have shown promise, but further studies fail to confirm meaningful clinical benefits such as improved survival or quality of life.
Manufacturing or Quality Issues: Problems with drug production or contamination can lead to withdrawal.
Changes in Treatment Standards: Newer, more effective therapies may render an approved drug obsolete or less favorable.
When a drug is withdrawn, patients currently receiving it may face uncertainty and disruption in their treatment plans. For some, the drug may have been their last hope, making withdrawal particularly distressing.
The Regulatory Process for Drug Approval and Withdrawal
The regulatory pathway for oncology drugs involves several stages:
Preclinical Testing: Laboratory and animal studies assess safety and biological activity.
Clinical Trials (Phases 1-3): Human trials evaluate safety, dosing, and efficacy.
Regulatory Review and Approval: Agencies like the FDA (U.S. Food and Drug Administration) or EMA (European Medicines Agency) review trial data before granting approval.
Post-Market Surveillance: After approval, ongoing studies and real-world data collection monitor long-term safety and effectiveness.
If post-market trials reveal new risks or lack of benefit, regulatory agencies may initiate a review that can lead to:
Label Changes: Warnings or restrictions on use.
Market Withdrawal: Complete removal of the drug from the market.
This process aims to protect patients but can be complex and slow, sometimes leading to delays in addressing emerging safety issues.
Case Studies of Withdrawn Oncology Drugs
Some specific examples of popular drugs that have either been withdrawn from the market completely or whose approval has been withdrawn from treating a specific patient population are listed below:
Bevacizumab (Avastin) was first approved by the FDA in February 2004 for the treatment of advanced colon cancer and has was susbequently approved for advanced lung (2006), kidney and brain (glioblastoma) cancers in 2009. Avastin was also approved for metastatic breast cancer in 2008 under the FDAs Accelerated Approval Program. In the E2100 clinical trial.
The E2100 trial was an open-label, randomized clinical trial that enrolled 722 patients who had not previously received chemotherapy for their locally recurrent or metastatic breast cancer. The patients were randomized (1:1) into groups of patients who received paclitaxel as a single agent or paclitaxel in combination with Avastin. The primary efficacy endpoint used in the study was progression free survival (PFS).
The secondary endpoints were overall survival (OS), objective response rate (ORR), duration of objective response, and quality of life (QOL).
Table 1. Results from the E2100 clinical trial.
Study arm | Median PFS (months) | Median OS (months) | ORR |
Paclitaxel + Avastin | 11.3 | 26.5 | 48.9% |
Paclitaxel | 5.8 | 24.8 | 22.2% |
Between-arm difference | 5.5 | 1.7 | 26.7% |
Hazard ratio (95% CI) | 0.48 (0.39–0.61) p < 0.0001 | 0.87 (0.72–1.05) p = 0.137 | (18.4%, 35%) p < 0001 |
CI = confidence interval; ORR = objective response rate; OS = overall survival; PFS = progression free survival.
Avastin was approved in combination with paclitaxel based on PFS, which was statistically significant with a 5.5 month improvement in PFS.
Avastin's accelerated approval was predicated on the submission of data from the placebo-controlled trials (AVADO and RIBBON 1) to confirm and support Avastin’s PFS benefit.
Table 2. AVADO and RIBBON 1 results
Study arm | Median PFS (months) | Median OS (months) | ORR |
AVADO | |||
Docetaxel + Avastin 15 mg/kg | 8.8 | 3.2 | 63.1% |
Docetaxel + Placebo | 7.9 | 31.9 | 44.4% |
Between-arm difference | 0.9 | −1.7 | 18.7% |
Hazard ratio (95% CI) | 0.62 (0.48–0.79) p = 0.0003 | 1.00 (0.76–1.32) p = 0.98 | (9.0%, 28.4%) p = 0.001 |
Docetaxel + Avastin 7.5 mg/kg | 8.7 | 30.8 | 55.2% |
Docetaxel + Placebo | 7.9 | 31.9 | 44.4% |
Between-arm difference | 0.8 | −1.1 | 10.8% |
Hazard ratio (95% CI) | 0.70 (0.55–0.90) p = 0.0054 | 1.10 (0.84–1.45) p = 0.48 | (9.0%, 20.7%) p = 0.0295 |
| |||
RIBBON 1 | |||
Taxene/Anthracycline + Avastin | 9.2 | 27.5 | 51.3% |
Taxene/Anthracycline + Placebo | 8.0 | NR | 37.9% |
Between-arm difference | 1.2 | NR | 13.5% |
Hazard ratio (95% CI) | 0.64 (0.52–0.80) p < 0.0001 | 1.11 (0.86–1.43) p = 0.44 | (4.6%, 22.3%) p = 0.0054 |
Capecitabine + Avastin | 8.6 | 25.7 | 35.4% |
Capecitabine + Placebo | 5.7 | 22.8 | 23.6% |
Between-arm difference | 2.9 | 2.9 | 11.8% |
Hazard ratio (95% CI) | 0.69 (0.56–0.84) p = 0.0002 | 0.88 (0.69–1.13) | (3.4%, 26.2%) p = 0.0097 |
CI = confidence interval; NR = not reached; ORR = objective response rate; OS = overall survival
Based on the data from the AVADO and Ribbon 1 trials, the FDA voted in November 2011 to withdraw Avastin's accelerated approval in metastatic breast cancer patients.
Sacituzumab govitecan (Trodelvy)
Trodelvy received accelerated approval for urethral cancer patients in the TROPHY-U-01 phase 2 clinical trial April 2021 but a confirmatory phase 3 trial, TROPICS-04, failed to show an improvement in overall survival.
Table 3. Comparison between the TROPHY-U-01 and TROPICS-04 clinical trials
Characteristic | TROPHY-U-01 | TROPICS-04 |
Clinical trial number | NCT03547973 | NCT04527991 |
Phase | Phase II | Phase III |
Purpose | Registrational study supporting accelerated approval | Confirmatory trial required by FDA to verify clinical benefit |
Study design | Open-label, single-arm, multicenter | Open-label, randomized (1:1), global, multicenter |
Patients enrolled | 113 (Cohort 1) | 711 |
Population | Locally advanced/unresectable or metastatic urothelial carcinoma progressing after platinum chemotherapy and checkpoint inhibitor | Similar population: advanced/metastatic urothelial carcinoma after platinum chemotherapy and PD-1/PD-L1 inhibitor |
Experimental treatment | Trodelvy 10 mg/kg Days 1 & 8 every 21 days | Trodelvy 10 mg/kg Days 1 & 8 every 21 days |
Control arm | None | Physician's choice chemotherapy (paclitaxel, docetaxel, or vinflunine) |
Primary endpoint | Objective Response Rate (ORR) | Overall Survival (OS) |
Secondary endpoints | DoR, PFS, OS, safety | PFS, ORR, safety, DoR |
Median follow-up | 9.1 months | 9.2 months |
Objective Response Rate (ORR) | 27% (31/113) | 23% vs 14% (chemotherapy) |
Median Duration of Response (DoR) | 7.2 months | Improved numerically but secondary endpoint |
Median PFS | 5.4 months | 4.2 months vs 3.6 months (HR 0.86; 95% CI 0.72–1.03) |
Median OS | 10.9 months | 10.3 months vs 9.0 months (HR 0.86; 95% CI 0.73–1.02; P=0.087) |
Primary endpoint met? | Yes | No |
Key efficacy conclusion | Demonstrated clinically meaningful activity in heavily pretreated patients | Failed to demonstrate statistically significant improvement in overall survival |
Safety observations | Grade ≥3 neutropenia (35%), leukopenia (18%), anemia (14%), diarrhea (10%), febrile neutropenia (10%); treatment discontinuation due to TRAEs: 6% | Higher number of deaths due to adverse events than chemotherapy, primarily early neutropenic complications and infections; overall safety profile otherwise generally consistent with known Trodelvy toxicities |
Regulatory outcome | Supported FDA accelerated approval (April 13, 2021) | Led Gilead to voluntarily withdraw the urothelial cancer indication; FDA withdrawal became effective November 22, 2024 |
In tables 1 and 2, I have provided a list of biologics and small molecules that have altered the patient populations treated by these drugs or had to completely withdraw the drugs from the market based on these post market approval clinical trials. For a complete list see the FDA's list: https://www.fda.gov/drugs/resources-information-approved-drugs/withdrawn-cancer-accelerated-approvals
Table 4. Biologics
Generic Name | Brand Name | Drug Class | Company | All FDA-Approved Tumor Types (at time of withdrawal) | Withdrawn Tumor Type / Indication | Initial Approval Date (Withdrawn Indication) | Withdrawal Date | Key Confirmatory Trial | Primary Issue | Withdrawal Driver | Scope of Withdrawal |
Gemtuzumab ozogamicin | Mylotarg | Anti-CD33 ADC (calicheamicin payload) | Pfizer / Wyeth | AML | Relapsed AML in CD33+ patients ≥60 years (monotherapy) | May 2000 (AA) | Jun-10 | SWOG S0106 (Phase 3) | No OS benefit over standard chemotherapy; excess early fatal veno-occlusive disease and bleeding | 🟡 Mixed | ⚠️ INDICATION ✅ RE-APPROVED Sep 2017 (lower dose; ALFA-0701 / AAML0531) |
Bevacizumab | Avastin | Anti-VEGF monoclonal antibody | Genentech / Roche | CRC, NSCLC, RCC, GBM, cervical, ovarian | Metastatic HER2-negative breast cancer (1st-line + paclitaxel) | Feb 2008 (AA) | Nov-11 | E2100; AVADO; RIBBON-1 | PFS benefit not confirmed across multiple trials; no OS improvement; unfavourable toxicity profile in mBC | 🔴 Efficacy | ⚠️ INDICATION (CRC, NSCLC, RCC, GBM, cervical, ovarian retained) |
Panobinostat | Farydak | Pan-HDAC inhibitor | Novartis → Secura Bio | Multiple myeloma (only approved indication) | RRMM + bortezomib + dexamethasone (≥2 prior regimens incl. bortezomib + IMiD) | Feb 2015 (AA) | ~2019–2022 | PANORAMA-1 (Phase 3) | OS benefit not confirmed in long-term follow-up; severe prohibitive toxicity (diarrhea, thrombocytopenia, cardiotoxicity) | 🟡 Mixed | ❌ ENTIRELY |
Pembrolizumab | Keytruda | PD-1 checkpoint inhibitor | Merck | Melanoma, NSCLC, HNSCC, CRC (MSI-H), gastric, many others | Urothelial carcinoma — 2L, PD-L1+ (CPS ≥10), post-platinum monotherapy | May 2017 (AA) | Dec-18 | KEYNOTE-045 (PD-L1 subgroup) | OS not confirmed in PD-L1-high biomarker-selected UC subset | 🔴 Efficacy | ⚠️ INDICATION |
Atezolizumab | Tecentriq | PD-L1 checkpoint inhibitor | Genentech / Roche | NSCLC, SCLC, HCC, BTC | Urothelial carcinoma — 2L, post-platinum (monotherapy) | May 2016 (AA) | Apr-21 | IMvigor211 (Phase 3) | OS vs. chemotherapy not statistically significant in platinum-refractory UC | 🔴 Efficacy | ⚠️ INDICATION |
Atezolizumab | Tecentriq | PD-L1 checkpoint inhibitor | Genentech / Roche | NSCLC, SCLC, HCC, BTC | NSCLC — 1L, PD-L1 high (TC ≥50% or IC ≥10%), monotherapy, no EGFR/ALK | Oct 2016 (AA) | Aug-21 | IMpower110 (Phase 3) | OS benefit not robustly confirmed in PD-L1-high subset | 🔴 Efficacy | ⚠️ INDICATION |
Atezolizumab | Tecentriq | PD-L1 checkpoint inhibitor | Genentech / Roche | NSCLC, SCLC, HCC, BTC | mTNBC — 1L, PD-L1+ (IC ≥1%) + nab-paclitaxel | Mar 2019 (AA) | Nov-21 | IMpassion131 (Phase 3) | Both PFS and OS endpoints not met; inconsistent with IMpassion130 data | 🔴 Efficacy | ⚠️ INDICATION |
Nivolumab | Opdivo | PD-1 checkpoint inhibitor | Bristol-Myers Squibb | Melanoma, NSCLC, RCC, cHL, HCC, MSI-H CRC, ESCC, GC, MPM, others | SCLC — 3rd-line or later (≥3 prior lines) | Aug 2018 (AA) | Dec-20 | CheckMate-331 (Phase 3) | OS vs. chemotherapy not statistically significant in unselected SCLC | 🔴 Efficacy | ⚠️ INDICATION |
Nivolumab | Opdivo | PD-1 checkpoint inhibitor | Bristol-Myers Squibb | Melanoma, NSCLC, RCC, cHL, HCC, MSI-H CRC, ESCC, GC, others | HCC — 2nd-line, post-sorafenib monotherapy | Sep 2017 (AA) | Aug-21 | CheckMate-459 (Phase 3) | OS vs. sorafenib not statistically significant | 🔴 Efficacy | ⚠️ INDICATION (combination with ipilimumab retained) |
Nivolumab | Opdivo | PD-1 checkpoint inhibitor | Bristol-Myers Squibb | Multiple | Gastric/GEJ adenocarcinoma — 3rd-line or later | Jun 2017 (AA) | Aug-21 | ATTRACTION-2 (US confirmatory data not submitted) | US-specific confirmatory evidence not generated; label superseded by combination data | 🔵 Submission | ⚠️ INDICATION (1L combinations retained) |
Pembrolizumab | Keytruda | PD-1 checkpoint inhibitor | Merck | Multiple | SCLC — 2nd-line or later (≥2 prior lines incl. platinum + topotecan) | Jun 2019 (AA) | Dec-20 | KEYNOTE-158 (Phase 2 single-arm) | Durable OS benefit not verified; confirmatory data insufficient | 🔴 Efficacy | ⚠️ INDICATION |
Pembrolizumab | Keytruda | PD-1 checkpoint inhibitor | Merck | Multiple | HCC — 2nd-line, post-sorafenib monotherapy | Nov 2018 (AA) | Apr-21 | KEYNOTE-240 (Phase 3) | OS and PFS co-primary endpoints did not meet pre-specified statistical boundary | 🔴 Efficacy | ⚠️ INDICATION |
Pembrolizumab | Keytruda | PD-1 checkpoint inhibitor | Merck | Multiple | Gastric/GEJ adenocarcinoma — 3L+, PD-L1+ (CPS ≥1), monotherapy | Sep 2017 (AA) | Jul-21 | KEYNOTE-061 (Phase 3) | OS vs. paclitaxel not met in 2L gastric setting | 🔴 Efficacy | ⚠️ INDICATION |
Pembrolizumab | Keytruda | PD-1 checkpoint inhibitor | Merck | Multiple | Colorectal cancer — 2L+, PD-L1+ (non-MSI-H/dMMR population) | Jun 2017 (AA) | Jul-21 | KEYNOTE-164; KEYNOTE-158 | No clinical benefit in PD-L1+ but non-MSI-H CRC | 🔴 Efficacy | ⚠️ INDICATION (MSI-H/dMMR CRC retained) |
Pembrolizumab | Keytruda | PD-1 checkpoint inhibitor | Merck | Multiple | Endometrial carcinoma — 2L+, non-MSI-H, post-chemotherapy monotherapy | Sep 2019 (AA) | Jul-21 | KEYNOTE-158 (non-MSI-H cohort) | No confirmed benefit in non-MSI-H endometrial cancer subset | 🔴 Efficacy | ⚠️ INDICATION (MSI-H and + lenvatinib retained) |
Pembrolizumab | Keytruda | PD-1 checkpoint inhibitor | Merck | Multiple | Esophageal/GEJ squamous — 2L+, PD-L1+ monotherapy | Jul 2019 (AA) | Jul-21 | KEYNOTE-180; KEYNOTE-181 (subgroup) | Clinical benefit not verified for labeled patient population | 🔴 Efficacy | ⚠️ INDICATION (1L combinations retained) |
Durvalumab | Imfinzi | PD-L1 checkpoint inhibitor | AstraZeneca | NSCLC (Stage III), BTC | Urothelial carcinoma — 2L, post-platinum, locally advanced/metastatic | May 2017 (AA) | Mar-20 | DANUBE (Phase 3) | OS not confirmed vs. chemotherapy in post-platinum UC | 🔴 Efficacy | ⚠️ INDICATION (Stage III NSCLC, BTC retained) |
Avelumab | Bavencio | PD-L1 checkpoint inhibitor | Pfizer / EMD Serono | Urothelial carcinoma (maintenance 1L), MCC | Urothelial carcinoma — 2L, post-platinum monotherapy | May 2017 (AA) | Apr-20 | JAVELIN Bladder 100 (post-platinum subgroup) | Clinical benefit not verified in platinum-refractory 2L UC setting | 🔴 Efficacy | ⚠️ INDICATION (1L maintenance UC retained) |
Belantamab mafodotin | Blenrep | Anti-BCMA ADC (MMAF auristatin payload) | GSK / Seagen | Multiple myeloma | RRMM — ≥4 prior lines (incl. PI, IMiD, anti-CD38 mAb) monotherapy | Aug 2020 (AA) | Nov-22 | DREAMM-3 (Phase 3) | PFS not statistically superior vs. pomalidomide + dexamethasone in randomised trial | 🔴 Efficacy | ⚠️ INDICATION ✅ RE-APPROVED May 2024 (DREAMM-7: + bortezomib + dex; DREAMM-8: + pomalidomide + dex) |
Sacituzumab govitecan | Trodelvy | TROP-2-directed ADC (SN-38 topoisomerase I inhibitor payload) | Gilead Sciences | mTNBC (multiple lines), HR+/HER2− BC | Locally advanced or metastatic urothelial carcinoma — post-platinum (post-CPI) | Apr 2021 (AA) | Nov-24 | TROPiCS-04 (Phase 3 randomised confirmatory) — sacituzumab govitecan vs. standard chemotherapy in previously treated metastatic UC; primary endpoint: OS | OS improvement vs. standard chemotherapy not statistically demonstrated l | 🔴 Efficacy | ⚠️ INDICATION (all breast cancer indications retained and expanded Jun 2026 |
Tositumomab + ¹³¹I-tositumomab | Bexxar | Anti-CD20 radioimmuno therapy | GlaxoSmithKline | Relapsed/refractory CD20+ follicular NHL (only indication) | Follicular NHL — relapsed/refractory (sole indication) | Jun 2003 (full approval) | Feb-14 | Commercial factors; confirmatory data not robustly pursued | Clinical benefit insufficiently confirmed; commercial non-viability; voluntary market discontinuation | 🔵 Commercial | ❌ ENTIRELY |
Table 5. Small molecules
Generic Name | Brand Name | Drug Class | Company | All FDA-Approved Tumor Types (at time of withdrawal) | Withdrawn Tumor Type / Indication | Initial Approval Date (Withdrawn Indication) | Withdrawal Date | Key Confirmatory Trial | Primary Issue | Withdrawal Driver | Scope of Withdrawal |
Gefitinib | Iressa | EGFR TKI (1st generation) | AstraZeneca | NSCLC (unselected) | NSCLC — unselected all-comer patient population (monotherapy) | May 2003 (AA) | Jun-05 | ISEL; INTACT 1 & 2 | OS benefit not demonstrated in unselected NSCLC; no biomarker-defined population at time of approval | 🔴 Efficacy | ⚠️ INDICATION ✅ RE-APPROVED Feb 2015 (EGFR mutation-positive NSCLC) |
Panobinostat | Farydak | Pan-HDAC inhibitor | Novartis → Secura Bio | Multiple myeloma (only approved indication) | RRMM + bortezomib + dexamethasone (≥2 prior regimens incl. bortezomib + IMiD) | Feb 2015 (AA) | ~2019–2022 | PANORAMA-1 (Phase 3) | OS benefit not confirmed in long-term follow-up; severe prohibitive toxicity (diarrhea, thrombocytopenia, cardiotoxicity) | 🟡 Mixed | ❌ ENTIRELY |
Idelalisib | Zydelig | PI3Kδ inhibitor | Gilead Sciences | CLL/SLL (with rituximab, restricted), FL | FL (≥2 prior therapies) AND SLL (≥2 prior therapies) — multiple indications withdrawn | Jul 2014 (AA) | 2022–2023 | Multiple post-market trials (DFS-017; ZEAL; ZENITH) | Fatal immune-mediated toxicities (fatal infections, hepatotoxicity, pneumonitis, colitis); mortality imbalances | 🟠 Safety | ⚠️ INDICATION (CLL + rituximab retained with boxed warning and REMS) |
Vincristine Sulfate Liposomal | Marqibo | Liposomal cytotoxic chemotherapy (sphingomyelin/cholesterol-encapsulated vinca alkaloid; microtubule inhibitor) | Acrotech Biopharma (fmr. Spectrum) | ALL | Ph− adult ALL — 2nd relapse or ≥2 prior lines monotherapy | Aug 2012 (AA) | Oct-22 | HALLMARK (Phase 3) | OS benefit vs. standard vincristine-containing regimens not demonstrated in randomised confirmatory trial | 🔴 Efficacy | ❌ ENTIRELY |
Umbralisib | Ukoniq | PI3Kδ / CK1ε dual inhibitor | TG Therapeutics | MZL, Follicular Lymphoma | MZL (≥1 prior anti-CD20) AND FL (≥3 prior lines) — both accelerated indications | Feb 2021 (AA) | Jun-22 | UNITY-CLL (randomised; cross-indication safety signal) | Statistically significant increase in all-cause mortality in UNITY-CLL; FDA extended safety concern to MZL/FL | 🟠 Safety (OS harm) | ❌ ENTIRELY |
Palbociclib | Ibrance | CDK4/6 inhibitor | Pfizer | HR+/HER2− breast cancer (female patients) | HR+/HER2− metastatic breast cancer — male patients only | Apr 2019 (AA — male-specific) | Mar-22 | Confirmatory data for male population not submitted | Clinical benefit in male patients not verified; confirmatory data not submitted within required period | 🔵 Submission | ⚠️ INDICATION (female HR+/HER2− fully retained) |
Copanlisib | Aliqopa | PI3Kα/δ inhibitor | Bayer | FL (only approved indication) | FL — ≥2 prior anti-neoplastic therapies (sole indication) | Sep 2017 (AA; converted 2019) | 2023 | CHRONOS-3 (Phase 3) | Clinical benefit not confirmed in confirmatory setting; Bayer voluntarily discontinued US commercialization | 🔴 Efficacy | ❌ ENTIRELY |
Duvelisib | Copiktra | PI3Kδ/γ dual inhibitor | Verastem / Secura Bio | CLL/SLL, FL | FL (≥2 prior lines) AND CLL/SLL indications | Sep 2018 (AA) | 2023–2024 | NAVIGATE (Phase 2 confirmatory); multiple safety studies | Fatal immune-mediated toxicities (infections, colitis, pneumonitis, hepatotoxicity); mortality imbalance across indications | 🟠 Safety | ❌ ENTIRELY (drug commercially discontinued from US market) |
Mobocertinib | Exkivity | EGFR Exon 20 Insertion-selective TKI | Takeda | NSCLC (only approved indication) | NSCLC with EGFR exon 20 insertion mutations — post-platinum (sole indication) | Sep 2021 (AA) | Oct-23 | EXCLAIM-2 (Phase 3) | PFS superiority vs. platinum-based chemotherapy not demonstrated in randomised Phase 3 | 🔴 Efficacy | ❌ ENTIRELY |
Zandelisib | — | PI3Kδ inhibitor | MEI Pharma / TG Therapeutics | FL, MZL (only approved indications) | FL/MZL — ≥2 prior lines (only indications) | Sep 2023 (AA) | Jun-24 | COASTAL (Phase 3) | Hepatotoxicity, excess all-cause mortality, and lack of confirmed efficacy benefit | 🟡 Mixed | ❌ ENTIRELY |
Selinexor | Xpovio | XPO1 / nuclear export inhibitor (SINE compound) | Karyopharm Therapeutics | Multiple myeloma (XVd; Xd — both retained) | DLBCL — relapsed/refractory, ≥2 prior lines monotherapy | Jun 2020 (AA) | Apr-26 | XPORT-DLBCL-030 (Phase 3) | OS and PFS benefit not demonstrated in randomised Phase 3 confirmatory trial | 🔴 Efficacy | ⚠️ INDICATION (both MM indications fully retained per OpenFDA NDA212306) |
Perspectives from Healthcare Professionals and Patients
Healthcare Professionals
Oncologists often experience tension between hope and caution. They want to offer the best available treatments but must balance this with emerging evidence. Withdrawal of a drug can:
Disrupt treatment plans.
Require rapid adaptation to alternative therapies.
Raise concerns about the reliability of initial approval data.
Many clinicians advocate for stronger post-market surveillance and more transparent communication from regulatory bodies.
Patients
For patients, drug withdrawal can feel like lost hope or betrayal. Many invest emotionally and physically in a treatment only to learn it is no longer available. Patients emphasize the need for:
Clear explanations about why a drug is withdrawn.
Support in transitioning to other treatments.
Inclusion in decision-making processes.
Patient advocacy groups often call for better safety monitoring and faster responses to emerging risks.
Future Considerations for Drug Safety and Efficacy in Oncology
The withdrawal of oncology drugs after approval highlights several areas for improvement:
Enhanced Post-Market Surveillance: Using real-world data and registries to detect safety signals earlier.
Adaptive Trial Designs: Allowing modifications based on interim results to reduce risks.
Personalized Medicine: Targeting drugs to patients most likely to benefit, reducing exposure to ineffective treatments.
Transparent Communication: Clear, timely updates from regulators and manufacturers to patients and providers.
Patient Involvement: Engaging patients in trial design and regulatory decisions to align with their needs and values.
These steps can help ensure that oncology drugs provide real benefits without exposing patients to unnecessary harm.
The withdrawal of approved oncology drugs after post-market trials presents significant challenges but also provides opportunities to improve cancer patient care. Understanding the reasons behind withdrawals, the regulatory processes involved, and the perspectives of those affected can guide better clinical practices. Ultimately, the goal is to deliver safe, effective treatments that improve outcomes and maintain trust between patients, healthcare providers, scientists and regulators.
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